LIVIVO - Search results -

Search results

Result 1 - 10 of total 46

Search options

Article ; Online: Condition-specific 3' mRNA isoform half-lives and stability elements in yeast.

Geisberg, Joseph V / Moqtaderi, Zarmik / Struhl, Kevin

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 18, Page(s) e2301117120

Abstract: Alternative polyadenylation generates numerous 3' mRNA isoforms that can differ in their stability, structure, and function. These isoforms can be used to map mRNA stabilizing and destabilizing elements within 3' untranslated regions (3'UTRs). Here, we ... ...

Abstract	Alternative polyadenylation generates numerous 3' mRNA isoforms that can differ in their stability, structure, and function. These isoforms can be used to map mRNA stabilizing and destabilizing elements within 3' untranslated regions (3'UTRs). Here, we examine how environmental conditions affect 3' mRNA isoform turnover and structure in yeast cells on a transcriptome scale. Isoform stability broadly increases when cells grow more slowly, with relative half-lives of most isoforms being well correlated across multiple conditions. Surprisingly, dimethyl sulfate probing reveals that individual 3' isoforms have similar structures across different conditions, in contrast to the extensive structural differences that can exist between closely related isoforms in an individual condition. Unexpectedly, most mRNA stabilizing and destabilizing elements function only in a single growth condition. The genes associated with some classes of condition-specific stability elements are enriched for different functional categories, suggesting that regulated mRNA stability might contribute to adaptation to different growth environments. Condition-specific stability elements do not result in corresponding condition-specific changes in steady-state mRNA isoform levels. This observation is consistent with a compensatory mechanism between polyadenylation and stability, and it suggests that condition-specific mRNA stability elements might largely reflect condition-specific regulation of mRNA 3' end formation.
MeSH term(s)	Saccharomyces cerevisiae/metabolism ; RNA Isoforms ; Transcription, Genetic ; Polyadenylation ; Protein Isoforms/genetics ; RNA, Messenger/metabolism ; 3' Untranslated Regions ; RNA Stability/genetics
Chemical Substances	RNA Isoforms ; Protein Isoforms ; RNA, Messenger ; 3' Untranslated Regions
Language	English
Publishing date	2023-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2301117120
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A compensatory link between cleavage/polyadenylation and mRNA turnover regulates steady-state mRNA levels in yeast.

Moqtaderi, Zarmik / Geisberg, Joseph V / Struhl, Kevin

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 4

Abstract: Cells have compensatory mechanisms to coordinate the rates of major biological processes, thereby permitting growth in a wide variety of conditions. Here, we uncover a compensatory link between cleavage/polyadenylation in the nucleus and messenger RNA ( ... ...

Abstract	Cells have compensatory mechanisms to coordinate the rates of major biological processes, thereby permitting growth in a wide variety of conditions. Here, we uncover a compensatory link between cleavage/polyadenylation in the nucleus and messenger RNA (mRNA) turnover in the cytoplasm. On a global basis, same-gene 3' mRNA isoforms with twofold or greater differences in half-lives have steady-state mRNA levels that differ by significantly less than a factor of 2. In addition, increased efficiency of cleavage/polyadenylation at a specific site is associated with reduced stability of the corresponding 3' mRNA isoform. This inverse relationship between cleavage/polyadenylation and mRNA isoform half-life reduces the variability in the steady-state levels of mRNA isoforms, and it occurs in all four growth conditions tested. These observations suggest that during cleavage/polyadenylation in the nucleus, mRNA isoforms are marked in a manner that persists upon translocation to the cytoplasm and affects the activity of mRNA degradation machinery, thus influencing mRNA stability.
MeSH term(s)	3' Untranslated Regions ; Polyadenylation ; RNA Cleavage ; RNA Isoforms ; RNA Stability ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Yeasts/genetics ; Yeasts/metabolism
Chemical Substances	3' Untranslated Regions ; RNA Isoforms ; RNA, Messenger
Language	English
Publishing date	2022-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2121488119
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Genome-wide oscillations in G + C density and sequence conservation.

Moqtaderi, Zarmik / Brown, Susan / Bender, Welcome

Genome research

2021 Volume 31, Issue 11, Page(s) 2050–2057

Abstract: Eukaryotic genomes typically show a uniform G + C content among chromosomes, but on smaller scales, many species have a G + C density that fluctuates with a characteristic wavelength. This oscillation is evident in many insect species, with wavelengths ... ...

Abstract	Eukaryotic genomes typically show a uniform G + C content among chromosomes, but on smaller scales, many species have a G + C density that fluctuates with a characteristic wavelength. This oscillation is evident in many insect species, with wavelengths ranging between 700 bp and 4 kb. Measures of evolutionary conservation oscillate in phase with G + C content, with conserved regions having higher G + C. Loci with large regulatory regions show more regular oscillations; coding sequences and heterochromatic regions show little or no oscillation. There is little oscillation in vertebrate genomes in regions with densely distributed mobile repetitive elements. However, species with few repeats show oscillation in both G + C density and sequence conservation. These oscillations may reflect optimal spacing of
MeSH term(s)	Base Sequence ; Biological Evolution ; Conserved Sequence/genetics ; Evolution, Molecular ; Genome ; Regulatory Sequences, Nucleic Acid ; Repetitive Sequences, Nucleic Acid
Language	English
Publishing date	2021-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.274332.120
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 8: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: 3' Untranslated Regions Are Modular Entities That Determine Polyadenylation Profiles.

Lui, Kai Hin / Geisberg, Joseph V / Moqtaderi, Zarmik / Struhl, Kevin

Molecular and cellular biology

2022 Volume 42, Issue 9, Page(s) e0024422

Abstract: The 3' ends of eukaryotic mRNAs are generated by cleavage of nascent transcripts followed by polyadenylation, which occurs at numerous sites within 3' untranslated regions (3' UTRs) but rarely within coding regions. An individual gene can yield many 3'- ... ...

Abstract	The 3' ends of eukaryotic mRNAs are generated by cleavage of nascent transcripts followed by polyadenylation, which occurs at numerous sites within 3' untranslated regions (3' UTRs) but rarely within coding regions. An individual gene can yield many 3'-mRNA isoforms with distinct half-lives. We dissect the relative contributions of protein-coding sequences (open reading frames [ORFs]) and 3' UTRs to polyadenylation profiles in yeast. ORF-deleted derivatives often display strongly decreased mRNA levels, indicating that ORFs contribute to overall mRNA stability. Poly(A) profiles, and hence relative isoform half-lives, of most (9 of 10) ORF-deleted derivatives are very similar to their wild-type counterparts. Similarly, in-frame insertion of a large protein-coding fragment between the ORF and 3' UTR has minimal effect on the poly(A) profile in all 15 cases tested. Last, reciprocal ORF/3'-UTR chimeric genes indicate that the poly(A) profile is determined by the 3' UTR. Thus, 3' UTRs are self-contained modular entities sufficient to determine poly(A) profiles and relative 3'-isoform half-lives. In the one atypical instance, ORF deletion causes an upstream shift of poly(A) sites, likely because juxtaposition of an unusually high AT-rich stretch directs polyadenylation closely downstream. This suggests that long AT-rich stretches, which are not encountered until after coding regions, are important for restricting polyadenylation to 3' UTRs.
MeSH term(s)	3' Untranslated Regions/genetics ; 5' Untranslated Regions ; Poly A/genetics ; Poly A/metabolism ; Polyadenylation ; Protein Isoforms/genetics ; RNA Isoforms/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism
Chemical Substances	3' Untranslated Regions ; 5' Untranslated Regions ; Protein Isoforms ; RNA Isoforms ; RNA, Messenger ; Poly A (24937-83-5)
Language	English
Publishing date	2022-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/mcb.00244-22
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Probing In Vivo Structure of Individual mRNA 3' Isoforms Using Dimethyl Sulfate.

Moqtaderi, Zarmik / Geisberg, Joseph V

Current protocols in molecular biology

2019 Volume 128, Issue 1, Page(s) e99

Abstract: The DMS region extraction and deep sequencing (DREADS) procedure was designed to probe RNA structure in vivo and to link this structural information to specific 3' isoforms. Growing cells are treated with the alkylating agent dimethyl sulfate (DMS), ... ...

Abstract	The DMS region extraction and deep sequencing (DREADS) procedure was designed to probe RNA structure in vivo and to link this structural information to specific 3' isoforms. Growing cells are treated with the alkylating agent dimethyl sulfate (DMS), which enters easily into cells and modifies RNA molecules at solvent-exposed A and C residues. RNA is isolated, and sequencing libraries are constructed in a manner that preserves the identities of individual mRNA isoforms arising from alternative cleavage/polyadenylation sites. During the cDNA synthesis step of library construction, the progress of reverse transcriptase (RT) is blocked when it encounters a DMS modification on the RNA, leading to disproportionate cDNA termination adjacent to DMS-modified positions. After paired-end deep sequencing, the downstream end of each sequenced fragment is mapped to a specific cleavage/poly(A) site representing an individual mRNA 3' isoform. The upstream mapped end of the sequenced fragment defines where the RT reaction stopped. Over the population of all sequenced fragments derived from a particular isoform, A and C positions that are overrepresented next to the upstream endpoints in the DMS sample (relative to a parallel untreated control) are inferred to have been DMS modified, and hence solvent exposed. This method thus allows in vivo structural information obtained using DMS to be linked to individual mRNA 3' isoforms. © 2019 by John Wiley & Sons, Inc.
MeSH term(s)	Gene Library ; Genetic Techniques ; High-Throughput Nucleotide Sequencing ; Nucleic Acid Conformation ; RNA Isoforms/chemistry ; RNA, Fungal/chemistry ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, RNA ; Sulfuric Acid Esters/chemistry
Chemical Substances	RNA Isoforms ; RNA, Fungal ; Sulfuric Acid Esters ; dimethyl sulfate (JW5CW40Z50)
Language	English
Publishing date	2019-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1934-3647
ISSN (online)	1934-3647
DOI	10.1002/cpmb.99
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

1994 A 523 -1-: Show issues
1994 A 523 -4-: Show issues
1994 A 523 -2-: Show issues
1994 A 523 -3-: Show issues

Order via subito

Details ▾

Article ; Online: Protein Binding to mRNA 3' Isoforms.

Geisberg, Joseph V / Moqtaderi, Zarmik

Current protocols in molecular biology

2019 Volume 128, Issue 1, Page(s) e101

Abstract: Here we describe CLIP-READS, a technique that combines elements of crosslinking and immunoprecipitation (CLIP) and 3' region extraction and deep sequencing (READS), to provide a genome-wide map of mRNA 3' isoform binding by a given messenger ... ...

Abstract	Here we describe CLIP-READS, a technique that combines elements of crosslinking and immunoprecipitation (CLIP) and 3' region extraction and deep sequencing (READS), to provide a genome-wide map of mRNA 3' isoform binding by a given messenger ribonucleoprotein (mRNP). In CLIP-READS, cells are grown to logarithmic phase and are irradiated with UV light (254 nm) to form RNA-protein adducts. The protein-mRNA complexes are immunoprecipitated from cell extracts with an antibody specific to the protein of interest, after which the protein component is digested away with Pronase. Messenger RNAs are then subjected to 3' READS. An input sample processed by 3' READS in parallel allows for the relative quantification of isoform-specific binding by the mRNP of interest. © 2019 by John Wiley & Sons, Inc.
MeSH term(s)	Binding Sites ; Cross-Linking Reagents ; High-Throughput Nucleotide Sequencing ; Immunoprecipitation ; Protein Binding ; RNA Isoforms/metabolism ; RNA, Fungal/chemistry ; RNA, Fungal/metabolism ; RNA, Messenger/chemistry ; RNA, Messenger/metabolism ; RNA-Binding Proteins/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Analysis, RNA
Chemical Substances	Cross-Linking Reagents ; RNA Isoforms ; RNA, Fungal ; RNA, Messenger ; RNA-Binding Proteins ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2019-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1934-3647
ISSN (online)	1934-3647
DOI	10.1002/cpmb.101
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

1994 A 523 -1-: Show issues
1994 A 523 -4-: Show issues
1994 A 523 -2-: Show issues
1994 A 523 -3-: Show issues

Order via subito

Details ▾

Article ; Online: Elongation rate of RNA polymerase II affects pausing patterns across 3' UTRs.

Khitun, Alexandra / Brion, Christian / Moqtaderi, Zarmik / Geisberg, Joseph V / Churchman, L Stirling / Struhl, Kevin

The Journal of biological chemistry

2023 Volume 299, Issue 11, Page(s) 105289

Abstract: Yeast mRNAs are polyadenylated at multiple sites in their 3' untranslated regions (3' UTRs), and poly(A) site usage is regulated by the rate of transcriptional elongation by RNA polymerase II (Pol II). Slow Pol II derivatives favor upstream poly(A) sites, ...

Abstract	Yeast mRNAs are polyadenylated at multiple sites in their 3' untranslated regions (3' UTRs), and poly(A) site usage is regulated by the rate of transcriptional elongation by RNA polymerase II (Pol II). Slow Pol II derivatives favor upstream poly(A) sites, and fast Pol II derivatives favor downstream poly(A) sites. Transcriptional elongation and polyadenylation are linked at the nucleotide level, presumably reflecting Pol II dwell time at each residue that influences the level of polyadenylation. Here, we investigate the effect of Pol II elongation rate on pausing patterns and the relationship between Pol II pause sites and poly(A) sites within 3' UTRs. Mutations that affect Pol II elongation rate alter sequence preferences at pause sites within 3' UTRs, and pausing preferences differ between 3' UTRs and coding regions. In addition, sequences immediately flanking the pause sites show preferences that are largely independent of Pol II speed. In wild-type cells, poly(A) sites are preferentially located < 50 nucleotides upstream from Pol II pause sites, but this spatial relationship is diminished in cells harboring Pol II speed mutants. Based on a random forest classifier, Pol II pause sites are modestly predicted by the distance to poly(A) sites but are better predicted by the chromatin landscape in Pol II speed derivatives. Transcriptional regulatory proteins can influence the relationship between Pol II pausing and polyadenylation but in a manner distinct from Pol II elongation rate derivatives. These results indicate a complex relationship between Pol II pausing and polyadenylation.
MeSH term(s)	3' Untranslated Regions/genetics ; Polyadenylation ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/genetics ; Mutation ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	3' Untranslated Regions ; RNA Polymerase II (EC 2.7.7.-) ; Transcription Factors ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2023-09-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.105289
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: 3′ Untranslated Regions Are Modular Entities That Determine Polyadenylation Profiles

Lui, Kai Hin / Geisberg, Joseph V. / Moqtaderi, Zarmik / Struhl, Kevin

Molecular and Cellular Biology. 2022 Sept. 1, v. 42, no. 9 p.e00244-22-

2022

Abstract: The 3′ ends of eukaryotic mRNAs are generated by cleavage of nascent transcripts followed by polyadenylation, which occurs at numerous sites within 3′ untranslated regions (3′ UTRs) but rarely within coding regions. An individual gene can yield many 3′- ... ...

Abstract	The 3′ ends of eukaryotic mRNAs are generated by cleavage of nascent transcripts followed by polyadenylation, which occurs at numerous sites within 3′ untranslated regions (3′ UTRs) but rarely within coding regions. An individual gene can yield many 3′-mRNA isoforms with distinct half-lives. We dissect the relative contributions of protein-coding sequences (open reading frames [ORFs]) and 3′ UTRs to polyadenylation profiles in yeast. ORF-deleted derivatives often display strongly decreased mRNA levels, indicating that ORFs contribute to overall mRNA stability. Poly(A) profiles, and hence relative isoform half-lives, of most (9 of 10) ORF-deleted derivatives are very similar to their wild-type counterparts. Similarly, in-frame insertion of a large protein-coding fragment between the ORF and 3′ UTR has minimal effect on the poly(A) profile in all 15 cases tested. Last, reciprocal ORF/3′-UTR chimeric genes indicate that the poly(A) profile is determined by the 3′ UTR. Thus, 3′ UTRs are self-contained modular entities sufficient to determine poly(A) profiles and relative 3′-isoform half-lives. In the one atypical instance, ORF deletion causes an upstream shift of poly(A) sites, likely because juxtaposition of an unusually high AT-rich stretch directs polyadenylation closely downstream. This suggests that long AT-rich stretches, which are not encountered until after coding regions, are important for restricting polyadenylation to 3′ UTRs.
Keywords	cell biology ; genes ; half life ; yeasts ; 3′ UTR ; 3′-end formation ; gene expression ; mRNA stability ; polyadenylation
Language	English
Dates of publication	2022-0901
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/mcb.00244-22
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The transcriptional elongation rate regulates alternative polyadenylation in yeast.

Geisberg, Joseph V / Moqtaderi, Zarmik / Struhl, Kevin

eLife

2020 Volume 9

Abstract: Yeast cells undergoing the diauxic response show a striking upstream shift in poly(A) site utilization, with increased use of ORF-proximal poly(A) sites resulting in shorter 3' mRNA isoforms for most genes. This altered poly(A) pattern is extremely ... ...

Abstract	Yeast cells undergoing the diauxic response show a striking upstream shift in poly(A) site utilization, with increased use of ORF-proximal poly(A) sites resulting in shorter 3' mRNA isoforms for most genes. This altered poly(A) pattern is extremely similar to that observed in cells containing Pol II derivatives with slow elongation rates. Conversely, cells containing derivatives with fast elongation rates show a subtle downstream shift in poly(A) sites. Polyadenylation patterns of many genes are sensitive to both fast and slow elongation rates, and a global shift of poly(A) utilization is strongly linked to increased purine content of sequences flanking poly(A) sites. Pol II processivity is impaired in diauxic cells, but strains with reduced processivity and normal Pol II elongation rates have normal polyadenylation profiles. Thus, Pol II elongation speed is important for poly(A) site selection and for regulating poly(A) patterns in response to environmental conditions.
MeSH term(s)	Poly A/genetics ; Poly A/metabolism ; Polyadenylation/genetics ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription Elongation, Genetic
Chemical Substances	Saccharomyces cerevisiae Proteins ; Poly A (24937-83-5) ; RNA Polymerase II (EC 2.7.7.-)
Language	English
Publishing date	2020-08-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.59810
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Nucleotide-level linkage of transcriptional elongation and polyadenylation.

Geisberg, Joseph V / Moqtaderi, Zarmik / Fong, Nova / Erickson, Benjamin / Bentley, David L / Struhl, Kevin

eLife

2022 Volume 11

Abstract: Alternative polyadenylation yields many mRNA isoforms whose 3' termini occur disproportionately in clusters within 3' untranslated regions. Previously, we showed that profiles of poly(A) site usage are regulated by the rate of transcriptional elongation ... ...

Abstract	Alternative polyadenylation yields many mRNA isoforms whose 3' termini occur disproportionately in clusters within 3' untranslated regions. Previously, we showed that profiles of poly(A) site usage are regulated by the rate of transcriptional elongation by RNA polymerase (Pol) II (Geisberg et al., 2020). Pol II derivatives with slow elongation rates confer an upstream-shifted poly(A) profile, whereas fast Pol II strains confer a downstream-shifted poly(A) profile. Within yeast isoform clusters, these shifts occur steadily from one isoform to the next across nucleotide distances. In contrast, the shift between clusters - from the last isoform of one cluster to the first isoform of the next - is much less pronounced, even over large distances. GC content in a region 13-30 nt downstream from isoform clusters correlates with their sensitivity to Pol II elongation rate. In human cells, the upstream shift caused by a slow Pol II mutant also occurs continuously at single nucleotide resolution within clusters but not between them. Pol II occupancy increases just downstream of poly(A) sites, suggesting a linkage between reduced elongation rate and cluster formation. These observations suggest that (1) Pol II elongation speed affects the nucleotide-level dwell time allowing polyadenylation to occur, (2) poly(A) site clusters are linked to the local elongation rate, and hence do not arise simply by intrinsically imprecise cleavage and polyadenylation of the RNA substrate, (3) DNA sequence elements can affect Pol II elongation and poly(A) profiles, and (4) the cleavage/polyadenylation and Pol II elongation complexes are spatially, and perhaps physically, coupled so that polyadenylation occurs rapidly upon emergence of the nascent RNA from the Pol II elongation complex.
MeSH term(s)	Humans ; Polyadenylation ; Nucleotides ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; Poly A/genetics ; Poly A/metabolism ; Saccharomyces cerevisiae/genetics ; 3' Untranslated Regions ; Transcription, Genetic
Chemical Substances	Nucleotides ; RNA Polymerase II (EC 2.7.7.-) ; Poly A (24937-83-5) ; 3' Untranslated Regions
Language	English
Publishing date	2022-11-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.83153
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito