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| Status |
Public on May 09, 2023 |
| Title |
A network of DZF proteins controls alternative splicing regulation and fidelity [RNA Bind-n-Seq] |
| Organism |
synthetic construct |
| Experiment type |
Other
|
| Summary |
Proteins containing DZF (domain associated with zinc fingers) modules play important roles throughout gene expression, from transcription to translation. Derived from nucleotidyltransferases but lacking catalytic residues, DZF domains serve as heterodimerization surfaces between DZF protein pairs. Three DZF proteins are widely expressed in mammalian tissues, ILF2, ILF3, and ZFR, which form mutually exclusive ILF2-ILF3 and ILF2-ZFR heterodimers. Using eCLIP-Seq, we find that ZFR binds across broad intronic regions to regulate the alternative splicing of cassette and mutually exclusive exons. ZFR preferentially binds dsRNA in vitro and is enriched on introns containing conserved dsRNA elements in cells. Many splicing events are similarly altered upon depletion of any of the three DZF proteins; however, we also identify independent and opposing roles for ZFR and ILF3 in alternative splicing regulation. Along with widespread involvement in cassette exon splicing, the DZF proteins control the fidelity and regulation of over a dozen highly validated mutually exclusive splicing events. Our findings indicate that the DZF protein complexes form a complex regulatory network that leverages dsRNA binding by ILF3 and ZFR to modulate splicing regulation and fidelity.
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| |
|
| Overall design |
RNA Bind-n-Seq of 6X-His tagged ZFRDZF/ILF2, ZFRlong/ILF2, and PTBP1
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| |
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| Contributor(s) |
Haque N, Will A, Cook AG, Hogg JR |
| Citation(s) |
37144502 |
| |
| Submission date |
Jun 14, 2022 |
| Last update date |
May 09, 2023 |
| Contact name |
J. Robert Hogg |
| E-mail(s) |
j.hogg@nih.gov
|
| Organization name |
National Heart, Lung, and Blood Institute
|
| Department |
Biochemistry and Biophysics Center
|
| Street address |
50 South Drive, Room 2341
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL27484 |
Illumina HiSeq 3000 (synthetic construct) |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE206061 |
A network of DZF proteins controls alternative splicing regulation and fidelity. |
|
| Relations |
| BioProject |
PRJNA848989 |
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