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Tytuł pozycji:

Discovery of a pre-mRNA structural scaffold as a contributor to the mammalian splicing code.

Tytuł:
Discovery of a pre-mRNA structural scaffold as a contributor to the mammalian splicing code.
Autorzy:
Saha K; Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Fernandez MM; Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Biswas T; Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Joseph S; Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Ghosh G; Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Źródło:
Nucleic acids research [Nucleic Acids Res] 2021 Jul 09; Vol. 49 (12), pp. 7103-7121.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural
Język:
English
Imprint Name(s):
Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
MeSH Terms:
RNA Splicing*
RNA Precursors/*chemistry
RNA, Messenger/*chemistry
HeLa Cells ; Humans ; Introns ; Mutation ; Nucleic Acid Conformation ; Protein Domains ; RNA Precursors/metabolism ; RNA Splice Sites ; RNA, Messenger/metabolism ; Ribonucleoprotein, U1 Small Nuclear/metabolism ; Serine-Arginine Splicing Factors/chemistry ; Serine-Arginine Splicing Factors/metabolism ; Splicing Factor U2AF/metabolism
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Grant Information:
R01 GM085490 United States GM NIGMS NIH HHS
Substance Nomenclature:
0 (RNA Precursors)
0 (RNA Splice Sites)
0 (RNA, Messenger)
0 (Ribonucleoprotein, U1 Small Nuclear)
0 (Splicing Factor U2AF)
170974-22-8 (Serine-Arginine Splicing Factors)
Entry Date(s):
Date Created: 20210623 Date Completed: 20210728 Latest Revision: 20210728
Update Code:
20240105
PubMed Central ID:
PMC8266590
DOI:
10.1093/nar/gkab533
PMID:
34161584
Czasopismo naukowe
The specific recognition of splice signals at or near exon-intron junctions is not explained by their weak conservation and instead is postulated to require a multitude of features embedded in the pre-mRNA strand. We explored the possibility of 3D structural scaffold of AdML-a model pre-mRNA substrate-guiding early spliceosomal components to the splice signal sequences. We find that mutations in the non-cognate splice signal sequences impede recruitment of early spliceosomal components due to disruption of the global structure of the pre-mRNA. We further find that the pre-mRNA segments potentially interacting with the early spliceosomal component U1 snRNP are distributed across the intron, that there is a spatial proximity of 5' and 3' splice sites within the pre-mRNA scaffold, and that an interplay exists between the structural scaffold and splicing regulatory elements in recruiting early spliceosomal components. These results suggest that early spliceosomal components can recognize a 3D structural scaffold beyond the short splice signal sequences, and that in our model pre-mRNA, this scaffold is formed across the intron involving the major splice signals. This provides a conceptual basis to analyze the contribution of recognizable 3D structural scaffolds to the splicing code across the mammalian transcriptome.
(© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

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