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| Status |
Public on Jul 05, 2022 |
| Title |
Cooperative engagement and subsequent selective displacement of SR proteins define the pre-mRNA 3D structural scaffold for early spliceosome assembly |
| Organism |
Human adenovirus 2 |
| Experiment type |
Other
|
| Summary |
We recently reported that serine-arginine-rich (SR) protein-mediated pre-mRNA structural remodeling generates a pre-mRNA 3D structural scaffold that is stably recognized by the early spliceosomal components. However, the intermediate steps between the free pre-mRNA and the assembled early spliceosome are not yet characterized. By probing the early spliceosomal complexes in vitro and RNA-protein interactions in vivo, we show that the SR proteins bind the pre-mRNAs cooperatively generating a substrate that recruits U1 snRNP and U2AF65 in a splice signal-independent manner. Excess U1 snRNP selectively displaces some of the SR protein molecules from the pre-mRNA generating the substrate for splice signal-specific, sequential recognition by U1 snRNP, U2AF65, and U2AF35. Our work thus identifies a novel function of U1 snRNP in mammalian splicing substrate definition, explains the need for excess U1 snRNP compared to other U snRNPs in vivo, demonstrates how excess SR proteins could inhibit splicing, and provides a conceptual basis to examine if this mechanism of splicing substrate definition is employed by other splicing regulatory proteins.
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| |
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| Overall design |
Refer to individual Series
|
| |
|
| Citation(s) |
35871302 |
| |
| Submission date |
Nov 11, 2021 |
| Last update date |
Jul 26, 2022 |
| Contact name |
Kaushik Saha |
| E-mail(s) |
ksaha79@googlemail.com
|
| Organization name |
University of California San Diego
|
| Department |
Chemistry and Biochemistry
|
| Lab |
NSB 3325A
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093-0375 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL30034 |
Illumina MiSeq (Human adenovirus 2) |
|
| Samples (22)
|
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| This SuperSeries is composed of the following SubSeries: |
| GSE188649 |
[SHAPE-MaP_4_mM] U1 snRNP regulates recruitment of early spliceosomal components by disrupting SRSF1-pre-mRNA interactions |
| GSE188650 |
[RNP-MaP] U1 snRNP regulates recruitment of early spliceosomal components by disrupting SRSF1-pre-mRNA interactions |
| GSE202785 |
[SHAPE-MaP_10_mM] U1 snRNP regulates recruitment of early spliceosomal components by disrupting SRSF1-pre-mRNA interactions |
|
| Relations |
| BioProject |
PRJNA779758 |
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