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  1. Article ; Online: The physiology of alternative splicing.

    Marasco, Luciano E / Kornblihtt, Alberto R

    Nature reviews. Molecular cell biology

    2022  Volume 24, Issue 4, Page(s) 242–254

    Abstract: Alternative splicing is a substantial contributor to the high complexity of transcriptomes of multicellular eukaryotes. In this Review, we discuss the accumulated evidence that most of this complexity is reflected at the protein level and fundamentally ... ...

    Abstract Alternative splicing is a substantial contributor to the high complexity of transcriptomes of multicellular eukaryotes. In this Review, we discuss the accumulated evidence that most of this complexity is reflected at the protein level and fundamentally shapes the physiology and pathology of organisms. This notion is supported not only by genome-wide analyses but, mainly, by detailed studies showing that global and gene-specific modulations of alternative splicing regulate highly diverse processes such as tissue-specific and species-specific cell differentiation, thermal regulation, neuron self-avoidance, infrared sensing, the Warburg effect, maintenance of telomere length, cancer and autism spectrum disorders (ASD). We also discuss how mastering the control of alternative splicing paved the way to clinically approved therapies for hereditary diseases.
    MeSH term(s) Alternative Splicing/genetics ; Genome-Wide Association Study ; Genome ; Transcriptome ; Neurons/metabolism
    Language English
    Publishing date 2022-10-13
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-022-00545-z
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  2. Article ; Online: Nuclear roles for Argonaute proteins in the control of flowering.

    Nazer, Ezequiel / Kornblihtt, Alberto R

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

    2021  Volume 118, Issue 52

    MeSH term(s) Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; RNA Interference ; RNA, Small Interfering
    Chemical Substances Argonaute Proteins ; RNA, Small Interfering
    Language English
    Publishing date 2021-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2120124118
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  3. Article ; Online: Epigenetics at the base of alternative splicing changes that promote colorectal cancer.

    Kornblihtt, Alberto R

    The Journal of clinical investigation

    2017  Volume 127, Issue 9, Page(s) 3281–3283

    Abstract: Chromatin modification influences gene expression by either repressing or activating genes, depending on the specific histone mark. Chromatin structure can also influence alternative splicing of transcripts; however, the mechanisms by which epigenetic ... ...

    Abstract Chromatin modification influences gene expression by either repressing or activating genes, depending on the specific histone mark. Chromatin structure can also influence alternative splicing of transcripts; however, the mechanisms by which epigenetic marks influence splicing are poorly understood. A report in the current issue of the JCI highlights the biological importance of the coordinated control of alternative pre-mRNA splicing by chromatin structure and transcriptional elongation. Yuan et al. found that mutation of the histone methyl transferase SEDT2 affects alternative splicing fates of several key regulatory genes, including those involved in Wnt signaling. As a consequence, loss of SEDT2 in the intestine aggravated Wnt/β-catenin signaling effects, thereby leading to colorectal cancer.
    MeSH term(s) Alternative Splicing ; Colorectal Neoplasms/genetics ; Epigenesis, Genetic ; Humans ; RNA Precursors/genetics ; RNA Splicing
    Chemical Substances RNA Precursors
    Language English
    Publishing date 2017-08-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI96497
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  4. Article ; Online: Linking transcription, RNA polymerase II elongation and alternative splicing.

    Giono, Luciana E / Kornblihtt, Alberto R

    The Biochemical journal

    2020  Volume 477, Issue 16, Page(s) 3091–3104

    Abstract: Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally ... ...

    Abstract Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic - such as promoter structure - and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.
    MeSH term(s) Alternative Splicing ; Animals ; Chromatin/genetics ; Gene Expression Regulation ; Humans ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; Transcription, Genetic
    Chemical Substances Chromatin ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2020-08-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20200475
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  5. Article ; Online: Transcriptional control of alternative splicing along time: ideas change, experiments remain.

    Kornblihtt, Alberto R

    RNA (New York, N.Y.)

    2015  Volume 21, Issue 4, Page(s) 670–672

    MeSH term(s) Alternative Splicing ; Transcription, Genetic
    Language English
    Publishing date 2015-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1241540-6
    ISSN 1469-9001 ; 1355-8382
    ISSN (online) 1469-9001
    ISSN 1355-8382
    DOI 10.1261/rna.051151.115
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    Zs.A 4777: Show issues Location:
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  6. Article ; Online: Seeking the truth behind the myth: Argonaute tales from "nuclearland".

    Nazer, Ezequiel / Gómez Acuña, Luciana / Kornblihtt, Alberto R

    Molecular cell

    2021  Volume 82, Issue 3, Page(s) 503–513

    Abstract: Argonaute proteins have been traditionally characterized as a highly evolutionary conserved family engaged in post-transcriptional gene silencing pathways. The Argonaute family is mainly grouped into the AGO and PIWI clades. The canonical role of ... ...

    Abstract Argonaute proteins have been traditionally characterized as a highly evolutionary conserved family engaged in post-transcriptional gene silencing pathways. The Argonaute family is mainly grouped into the AGO and PIWI clades. The canonical role of Argonaute proteins relies on their ability to bind small-RNAs that recognize complementary sequences on target mRNAs to induce either mRNA degradation or translational repression. However, there is an increasing amount of evidence supporting that Argonaute proteins also exert multiple nuclear functions that subsequently regulate gene expression. In this line, genome-wide studies showed that members from the AGO clade regulate transcription, 3D chromatin organization, and splicing of active loci located within euchromatin. Here, we discuss recent work based on high-throughput technologies that have significantly contributed to shed light on the multivariate nuclear functions of AGO proteins in different model organisms. We also analyze data supporting that AGO proteins are able to execute these nuclear functions independently from small RNA pathways. Finally, we integrate these mechanistic insights with recent reports highlighting the clinical importance of AGO in breast and prostate cancer development.
    MeSH term(s) Animals ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; Eukaryotic Initiation Factors/genetics ; Eukaryotic Initiation Factors/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; RNA Splicing ; Transcription, Genetic
    Chemical Substances AGO1 protein, human ; AGO2 protein, human ; Argonaute Proteins ; Chromatin ; Eukaryotic Initiation Factors
    Language English
    Publishing date 2021-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.11.005
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  7. Article ; Online: A long noncoding way to alternative splicing in plant development.

    Kornblihtt, Alberto R

    Developmental cell

    2014  Volume 30, Issue 2, Page(s) 117–119

    Abstract: In this issue of Developmental Cell, Bardou et al. (2014) elucidate how long, highly structured noncoding RNAs control alternative splicing regulators that specifically mediate the action of the hormone auxin in the promotion of lateral root growth in ... ...

    Abstract In this issue of Developmental Cell, Bardou et al. (2014) elucidate how long, highly structured noncoding RNAs control alternative splicing regulators that specifically mediate the action of the hormone auxin in the promotion of lateral root growth in Arabidopsis.
    MeSH term(s) Alternative Splicing ; Arabidopsis/genetics ; Arabidopsis Proteins/metabolism ; RNA, Long Noncoding/genetics
    Chemical Substances Arabidopsis Proteins ; Nsr1 protein, Arabidopsis ; RNA, Long Noncoding
    Language English
    Publishing date 2014-07-28
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2014.07.010
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  8. Article: Seeking the truth behind the myth: Argonaute tales from “nuclearland”

    Nazer, Ezequiel / Gómez Acuña, Luciana / Kornblihtt, Alberto R.

    Molecular cell. 2022 Feb. 03, v. 82, no. 3

    2022  

    Abstract: Argonaute proteins have been traditionally characterized as a highly evolutionary conserved family engaged in post-transcriptional gene silencing pathways. The Argonaute family is mainly grouped into the AGO and PIWI clades. The canonical role of ... ...

    Abstract Argonaute proteins have been traditionally characterized as a highly evolutionary conserved family engaged in post-transcriptional gene silencing pathways. The Argonaute family is mainly grouped into the AGO and PIWI clades. The canonical role of Argonaute proteins relies on their ability to bind small-RNAs that recognize complementary sequences on target mRNAs to induce either mRNA degradation or translational repression. However, there is an increasing amount of evidence supporting that Argonaute proteins also exert multiple nuclear functions that subsequently regulate gene expression. In this line, genome-wide studies showed that members from the AGO clade regulate transcription, 3D chromatin organization, and splicing of active loci located within euchromatin. Here, we discuss recent work based on high-throughput technologies that have significantly contributed to shed light on the multivariate nuclear functions of AGO proteins in different model organisms. We also analyze data supporting that AGO proteins are able to execute these nuclear functions independently from small RNA pathways. Finally, we integrate these mechanistic insights with recent reports highlighting the clinical importance of AGO in breast and prostate cancer development.
    Keywords breasts ; carcinogenesis ; chromatin ; data analysis ; gene expression ; genes ; prostatic neoplasms
    Language English
    Dates of publication 2022-0203
    Size p. 503-513.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.11.005
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  9. Article: Alternative Splicing and Transcription Elongation in Plants.

    Godoy Herz, Micaela A / Kornblihtt, Alberto R

    Frontiers in plant science

    2019  Volume 10, Page(s) 309

    Abstract: Alternative splicing and transcription elongation by RNA polymerase II (RNAPII) are two processes which are tightly connected. Splicing is a co-transcriptional process, and different experimental approaches show that splicing is coupled to transcription ... ...

    Abstract Alternative splicing and transcription elongation by RNA polymerase II (RNAPII) are two processes which are tightly connected. Splicing is a co-transcriptional process, and different experimental approaches show that splicing is coupled to transcription in
    Language English
    Publishing date 2019-03-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2711035-7
    ISSN 1664-462X
    ISSN 1664-462X
    DOI 10.3389/fpls.2019.00309
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  10. Article ; Online: CTCF: from insulators to alternative splicing regulation.

    Kornblihtt, Alberto R

    Cell research

    2012  Volume 22, Issue 3, Page(s) 450–452

    MeSH term(s) Alternative Splicing/genetics ; CCCTC-Binding Factor ; DNA/genetics ; DNA Methylation/genetics ; Humans ; Repressor Proteins/metabolism
    Chemical Substances CCCTC-Binding Factor ; CTCF protein, human ; Repressor Proteins ; DNA (9007-49-2)
    Language English
    Publishing date 2012-02-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 1319303-x
    ISSN 1748-7838 ; 1001-0602
    ISSN (online) 1748-7838
    ISSN 1001-0602
    DOI 10.1038/cr.2012.22
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