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  1. Article ; Online: Context-specific effects of sequence elements on subcellular localization of linear and circular RNAs.

    Ron, Maya / Ulitsky, Igor

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2481

    Abstract: Long RNAs vary extensively in their post-transcriptional fates, and this variation is attributed in part to short sequence elements. We used massively parallel RNA assays to study how sequences derived from noncoding RNAs influence the subcellular ... ...

    Abstract Long RNAs vary extensively in their post-transcriptional fates, and this variation is attributed in part to short sequence elements. We used massively parallel RNA assays to study how sequences derived from noncoding RNAs influence the subcellular localization and stability of circular and linear RNAs, including spliced and unspliced forms. We find that the effects of sequence elements strongly depend on the host RNA context, with limited overlap between sequences that drive nuclear enrichment of linear and circular RNAs. Binding of specific RNA binding proteins underpins some of these differences-SRSF1 binding leads to nuclear enrichment of circular RNAs; SAFB binding is associated with nuclear enrichment of predominantly unspliced linear RNAs; and IGF2BP1 promotes export of linear spliced RNA molecules. The post-transcriptional fate of long RNAs is thus dictated by combinatorial contributions of specific sequence elements, of splicing, and of the presence of the terminal features unique to linear RNAs.
    MeSH term(s) Cell Nucleus/genetics ; Cell Nucleus/metabolism ; RNA/genetics ; RNA/metabolism ; RNA Splicing/genetics ; RNA, Circular ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
    Chemical Substances RNA, Circular ; RNA-Binding Proteins ; RNA (63231-63-0)
    Language English
    Publishing date 2022-05-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30183-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Gene Architecture and Sequence Composition Underpin Selective Dependency of Nuclear Export of Long RNAs on NXF1 and the TREX Complex.

    Zuckerman, Binyamin / Ron, Maya / Mikl, Martin / Segal, Eran / Ulitsky, Igor

    Molecular cell

    2020  Volume 79, Issue 2, Page(s) 251–267.e6

    Abstract: The core components of the nuclear RNA export pathway are thought to be required for export of virtually all polyadenylated RNAs. Here, we depleted different proteins that act in nuclear export in human cells and quantified the transcriptome-wide ... ...

    Abstract The core components of the nuclear RNA export pathway are thought to be required for export of virtually all polyadenylated RNAs. Here, we depleted different proteins that act in nuclear export in human cells and quantified the transcriptome-wide consequences on RNA localization. Different genes exhibited substantially variable sensitivities, with depletion of NXF1 and TREX components causing some transcripts to become strongly retained in the nucleus while others were not affected. Specifically, NXF1 is preferentially required for export of single- or few-exon transcripts with long exons or high A/U content, whereas depletion of TREX complex components preferentially affects spliced and G/C-rich transcripts. Using massively parallel reporter assays, we identified short sequence elements that render transcripts dependent on NXF1 for their export and identified synergistic effects of splicing and NXF1. These results revise the current model of how nuclear export shapes the distribution of RNA within human cells.
    MeSH term(s) Active Transport, Cell Nucleus ; Animals ; Base Sequence ; Cell Line ; Cell Nucleus/metabolism ; Humans ; Mice ; Multiprotein Complexes/metabolism ; Nucleocytoplasmic Transport Proteins/physiology ; RNA/chemistry ; RNA/metabolism ; RNA Stability ; RNA Transport ; RNA-Binding Proteins/physiology ; RNA-Seq
    Chemical Substances Multiprotein Complexes ; NXF1 protein, human ; Nucleocytoplasmic Transport Proteins ; RNA-Binding Proteins ; RNA (63231-63-0)
    Language English
    Publishing date 2020-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2020.05.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Gene Architecture and Sequence Composition Underpin Selective Dependency of Nuclear Export of Long RNAs on NXF1 and the TREX Complex

    Zuckerman, Binyamin / Ron, Maya / Mikl, Martin / Segal, Eran / Ulitsky, Igor

    Molecular cell. 2020 July 16, v. 79, no. 2

    2020  

    Abstract: The core components of the nuclear RNA export pathway are thought to be required for export of virtually all polyadenylated RNAs. Here, we depleted different proteins that act in nuclear export in human cells and quantified the transcriptome-wide ... ...

    Abstract The core components of the nuclear RNA export pathway are thought to be required for export of virtually all polyadenylated RNAs. Here, we depleted different proteins that act in nuclear export in human cells and quantified the transcriptome-wide consequences on RNA localization. Different genes exhibited substantially variable sensitivities, with depletion of NXF1 and TREX components causing some transcripts to become strongly retained in the nucleus while others were not affected. Specifically, NXF1 is preferentially required for export of single- or few-exon transcripts with long exons or high A/U content, whereas depletion of TREX complex components preferentially affects spliced and G/C-rich transcripts. Using massively parallel reporter assays, we identified short sequence elements that render transcripts dependent on NXF1 for their export and identified synergistic effects of splicing and NXF1. These results revise the current model of how nuclear export shapes the distribution of RNA within human cells.
    Keywords RNA transport ; exons ; humans ; messenger RNA ; models ; proteins ; synergism
    Language English
    Dates of publication 2020-0716
    Size p. 251-267.e6.
    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.2020.05.013
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Massively parallel identification of mRNA localization elements in primary cortical neurons.

    Mendonsa, Samantha / von Kügelgen, Nicolai / Dantsuji, Sayaka / Ron, Maya / Breimann, Laura / Baranovskii, Artem / Lödige, Inga / Kirchner, Marieluise / Fischer, Meret / Zerna, Nadja / Bujanic, Lucija / Mertins, Philipp / Ulitsky, Igor / Chekulaeva, Marina

    Nature neuroscience

    2023  Volume 26, Issue 3, Page(s) 394–405

    Abstract: Cells adopt highly polarized shapes and form distinct subcellular compartments in many cases due to the localization of many mRNAs to specific areas, where they are translated into proteins with local functions. This mRNA localization is mediated by ... ...

    Abstract Cells adopt highly polarized shapes and form distinct subcellular compartments in many cases due to the localization of many mRNAs to specific areas, where they are translated into proteins with local functions. This mRNA localization is mediated by specific cis-regulatory elements in mRNAs, commonly called 'zipcodes'. Although there are hundreds of localized mRNAs, only a few zipcodes have been characterized. Here we describe a novel neuronal zipcode identification protocol (N-zip) that can identify zipcodes across hundreds of 3' untranslated regions. This approach combines a method of separating the principal subcellular compartments of neurons-cell bodies and neurites-with a massively parallel reporter assay. N-zip identifies the let-7 binding site and (AU)
    MeSH term(s) Mice ; Animals ; RNA, Messenger/metabolism ; Neurons/metabolism ; Neurites
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2023-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-022-01243-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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