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Article ; Online: Localization of

Norris, Megan L / Mendell, Joshua T

2023 Volume 37, Issue 5-6, Page(s) 191–203

Abstract: Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In nonneuronal cells, specific mRNAs localize to cell protrusions, and proper mRNA localization is required ... ...

Abstract	Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In nonneuronal cells, specific mRNAs localize to cell protrusions, and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show that
MeSH term(s)	RNA, Messenger/metabolism ; Proteins/metabolism ; Kinesins/genetics ; Kinesins/metabolism ; Dyneins/metabolism ; Cell Movement/genetics
Chemical Substances	RNA, Messenger ; Proteins ; Kinesins (EC 3.6.4.4) ; Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.350320.122
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Article: MicroRNA turnover: a tale of tailing, trimming, and targets.

Han, Jaeil / Mendell, Joshua T

Trends in biochemical sciences

2022 Volume 48, Issue 1, Page(s) 26–39

Abstract: MicroRNAs (miRNAs) post-transcriptionally repress gene expression by guiding Argonaute (AGO) proteins to target mRNAs. While much is known about the regulation of miRNA biogenesis, miRNA degradation pathways are comparatively poorly understood. Although ... ...

Abstract	MicroRNAs (miRNAs) post-transcriptionally repress gene expression by guiding Argonaute (AGO) proteins to target mRNAs. While much is known about the regulation of miRNA biogenesis, miRNA degradation pathways are comparatively poorly understood. Although miRNAs generally exhibit slow turnover, they can be rapidly degraded through regulated mechanisms that act in a context- or sequence-specific manner. Recent work has revealed a particularly important role for specialized target interactions in controlling rates of miRNA degradation. Engagement of these targets is associated with the addition and removal of nucleotides from the 3' ends of miRNAs, a process known as tailing and trimming. Here we review these mechanisms of miRNA modification and turnover, highlighting the contexts in which they impact miRNA stability and discussing important questions that remain unanswered.
MeSH term(s)	MicroRNAs/genetics ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; RNA Stability ; Nucleotides/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	MicroRNAs ; Argonaute Proteins ; Nucleotides ; RNA, Messenger
Language	English
Publishing date	2022-07-07
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	194216-5
ISSN	1362-4326 ; 0968-0004 ; 0376-5067
ISSN (online)	1362-4326
ISSN	0968-0004 ; 0376-5067
DOI	10.1016/j.tibs.2022.06.005
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Article ; Online: NORAD-induced Pumilio phase separation is required for genome stability.

Elguindy, Mahmoud M / Mendell, Joshua T

Nature

2021 Volume 595, Issue 7866, Page(s) 303–308

Abstract: Liquid-liquid phase separation is a major mechanism of subcellular ... ...

Abstract	Liquid-liquid phase separation is a major mechanism of subcellular compartmentalization
MeSH term(s)	Cell Line ; Cytoplasm/chemistry ; Cytoplasm/genetics ; Cytoplasm/metabolism ; Genomic Instability ; Humans ; Phase Transition ; RNA/chemistry ; RNA/genetics ; RNA/metabolism ; RNA, Long Noncoding/chemistry ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA-Binding Proteins/chemistry ; RNA-Binding Proteins/metabolism ; Transcription Factors/chemistry ; Transcription Factors/metabolism
Chemical Substances	NORAD long non-coding RNA, human ; RNA, Long Noncoding ; RNA-Binding Proteins ; Transcription Factors ; pumilio protein, human ; RNA (63231-63-0)
Language	English
Publishing date	2021-06-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-03633-w
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Article: MicroRNA turnover: a tale of tailing, trimming, and targets

Han, Jaeil / Mendell, Joshua T.

Trends in biochemical sciences. 2022,

2022

Abstract: MicroRNAs (miRNA) post-transcriptionally repress gene expression by guiding Argonaute proteins to target mRNAs. While much is known about regulation of miRNA biogenesis, miRNA degradation pathways are comparatively poorly understood. Although miRNAs ... ...

Abstract	MicroRNAs (miRNA) post-transcriptionally repress gene expression by guiding Argonaute proteins to target mRNAs. While much is known about regulation of miRNA biogenesis, miRNA degradation pathways are comparatively poorly understood. Although miRNAs generally exhibit slow turnover, they can be rapidly degraded through regulated mechanisms that act in a context or sequence-specific manner. Recent work has revealed a particularly important role for specialized target interactions in controlling rates of miRNA degradation. Engagement of these targets is associated with addition and removal of nucleotides from the 3′ ends of miRNAs, a process known as tailing and trimming. Here we review these mechanisms of miRNA modification and turnover, highlighting the contexts in which they impact miRNA stability and discussing important questions that remain unanswered.
Keywords	biogenesis ; gene expression ; microRNA ; nucleotides
Language	English
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	194220-7
ISSN	0968-0004 ; 0376-5067
ISSN	0968-0004 ; 0376-5067
DOI	10.1016/j.tibs.2022.06.005
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Antisense-Mediated Transcript Knockdown Triggers Premature Transcription Termination.

Lee, Jong-Sun / Mendell, Joshua T

Molecular cell

2020 Volume 77, Issue 5, Page(s) 1044–1054.e3

Abstract: Antisense oligonucleotides (ASOs) that trigger RNase-H-mediated cleavage are commonly used to knock down transcripts for experimental or therapeutic purposes. In particular, ASOs are frequently used to functionally interrogate long noncoding RNAs ( ... ...

Abstract	Antisense oligonucleotides (ASOs) that trigger RNase-H-mediated cleavage are commonly used to knock down transcripts for experimental or therapeutic purposes. In particular, ASOs are frequently used to functionally interrogate long noncoding RNAs (lncRNAs) and discriminate lncRNA loci that produce functional RNAs from those whose activity is attributable to the act of transcription. Transcription termination is triggered by cleavage of nascent transcripts, generally during polyadenylation, resulting in degradation of the residual RNA polymerase II (Pol II)-associated RNA by XRN2 and dissociation of elongating Pol II. Here, we show that ASOs act upon nascent transcripts and, consequently, induce premature transcription termination downstream of the cleavage site in an XRN2-dependent manner. Targeting the transcript 3' end with ASOs, however, allows transcript knockdown while preserving Pol II association with the gene body. These results demonstrate that the effects of ASOs on transcription must be considered for appropriate experimental and therapeutic use of these reagents.
MeSH term(s)	Chromatin/genetics ; Chromatin/metabolism ; Exoribonucleases/metabolism ; HCT116 Cells ; HEK293 Cells ; Humans ; Models, Genetic ; Oligonucleotides, Antisense/genetics ; Oligonucleotides, Antisense/metabolism ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; RNA Precursors/genetics ; RNA Precursors/metabolism ; RNA Stability ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Time Factors ; Transcription Termination, Genetic
Chemical Substances	Chromatin ; Oligonucleotides, Antisense ; RNA Precursors ; RNA, Messenger ; RNA Polymerase II (EC 2.7.7.-) ; Exoribonucleases (EC 3.1.-) ; XRN2 protein, human (EC 3.1.13.1)
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2019.12.011
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Zs.A 5055: Show issues

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Article ; Online: Targeting a Long Noncoding RNA in Breast Cancer.

Mendell, Joshua T

The New England journal of medicine

2016 Volume 374, Issue 23, Page(s) 2287–2289

MeSH term(s)	Animals ; Breast Neoplasms/genetics ; Breast Neoplasms/therapy ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; RNA, Long Noncoding/antagonists & inhibitors ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
Chemical Substances	MALAT1 long non-coding RNA, human ; Malat1 long non-coding RNA, mouse ; RNA, Long Noncoding
Language	English
Publishing date	2016-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcibr1603785
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Article ; Online: Target-directed microRNA degradation regulates developmental microRNA expression and embryonic growth in mammals.

Jones, Benjamin T / Han, Jaeil / Zhang, He / Hammer, Robert E / Evers, Bret M / Rakheja, Dinesh / Acharya, Asha / Mendell, Joshua T

Genes & development

2023 Volume 37, Issue 13-14, Page(s) 661–674

Abstract: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in development and disease. Target-directed miRNA degradation (TDMD), a pathway in which miRNAs that bind to specialized targets with extensive ... ...

Abstract	MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in development and disease. Target-directed miRNA degradation (TDMD), a pathway in which miRNAs that bind to specialized targets with extensive complementarity are rapidly decayed, has emerged as a potent mechanism of controlling miRNA levels. Nevertheless, the biological role and scope of miRNA regulation by TDMD in mammals remains poorly understood. To address these questions, we generated mice with constitutive or conditional deletion of
MeSH term(s)	Mice ; Animals ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Mammals/genetics ; Base Sequence
Chemical Substances	MicroRNAs
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.350906.123
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Article: Target-directed microRNA degradation regulates developmental microRNA expression and embryonic growth in mammals.

Jones, Benjamin T / Han, Jaeil / Zhang, He / Hammer, Robert E / Evers, Bret M / Rakheja, Dinesh / Acharya, Asha / Mendell, Joshua T

bioRxiv : the preprint server for biology

2023

Abstract	MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in development and disease. Target-directed miRNA degradation (TDMD), a pathway in which miRNAs that bind to specialized targets with extensive complementarity are rapidly decayed, has emerged as a potent mechanism of controlling miRNA levels. Nevertheless, the biological role and scope of miRNA regulation by TDMD in mammals remains poorly understood. To address these questions, we generated mice with constitutive or conditional deletion of
Language	English
Publishing date	2023-06-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.26.546601
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Article: Dissecting the biophysics and biology of intrinsically disordered proteins.

Banerjee, Priya R / Holehouse, Alex S / Kriwacki, Richard / Robustelli, Paul / Jiang, Hao / Sobolevsky, Alexander I / Hurley, Jennifer M / Mendell, Joshua T

Trends in biochemical sciences

2023 Volume 49, Issue 2, Page(s) 101–104

Abstract: Intrinsically disordered regions (IDRs) within human proteins play critical roles in cellular information processing, including signaling, transcription, stress response, DNA repair, genome organization, and RNA processing. Here, we summarize current ... ...

Abstract	Intrinsically disordered regions (IDRs) within human proteins play critical roles in cellular information processing, including signaling, transcription, stress response, DNA repair, genome organization, and RNA processing. Here, we summarize current challenges in the field and propose cutting-edge approaches to address them in physiology and disease processes, with a focus on cancer.
MeSH term(s)	Humans ; Intrinsically Disordered Proteins/metabolism ; Biophysics ; Biology
Chemical Substances	Intrinsically Disordered Proteins
Language	English
Publishing date	2023-11-08
Publishing country	England
Document type	Journal Article
ZDB-ID	194216-5
ISSN	1362-4326 ; 0968-0004 ; 0376-5067
ISSN (online)	1362-4326
ISSN	0968-0004 ; 0376-5067
DOI	10.1016/j.tibs.2023.10.002
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Article ; Online: Functional Classification and Experimental Dissection of Long Noncoding RNAs.

Kopp, Florian / Mendell, Joshua T

Cell

2018 Volume 172, Issue 3, Page(s) 393–407

Abstract: Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of ... ...

Abstract	Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bi-directional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology with great potential to advance our understanding of normal physiology and disease.
MeSH term(s)	Animals ; Humans ; RNA, Long Noncoding/classification ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Regulatory Sequences, Nucleic Acid ; Transcription, Genetic
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2018-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2018.01.011
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