PXD018090

PXD018090 is an original dataset announced via ProteomeXchange.

Title	SRSF7 and SRSF3 affectSRSF7 and SRSF3 affect 3’UTR length in opposite directions by controlling proximal poly(A)-site usage and CFIm levels 3’UTR length in opposite directions by controlling proximal poly(A)-site usage and CFIm levels
Description	Alternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which affects the length of their 3’ untranslated regions (3’UTRs). APA regulates stage- and tissue-specific gene expression by affecting the stability, subcellular localization or translation rate of transcripts. We have recently shown that SRSF3 and SRSF7, two closely related SR proteins, link APA to mRNA export. However, the underlying mechanism for APA regulation by SRSF3 and SRSF7 remained unknown. Here, we combined iCLIP and 3’-end sequencing to find that both proteins bind upstream of proximal PAS (pPAS), but exert opposing effects on 3’UTR length. We show that SRSF7 enhances pPAS usage in a splicing-independent and concentration-dependent manner by recruiting the cleavage factor FIP1, thereby generating short 3’UTRs. SRSF7-specific domains that are absent in SRSF3 are necessary and sufficient for FIP1 recruitment. SRSF3 promotes long 3’UTRs by maintaining high levels of the cleavage factor Im (CFIm) via alternative splicing. Using iCLIP, we show that CFIm binds before and after the pPASs of SRSF3 targets, which masks them and inhibits polyadenylation. In the absence of SRSF3, CFIm levels are strongly reduced, which exposes the pPASs and leads to shorter 3’UTRs. Conversely, during cellular differentiation, 3’UTRs are massively extended, while the levels of SRSF7 and FIP1 strongly decline. Altogether, our data suggest that SRSF7 acts as a sequence-specific enhancer of pPASs, while SRSF3 inhibits pPAS usage by controlling CFIm levels. Our data shed light on a long-standing puzzle of how one factor (CFIm) can inhibit and enhance PAS usage.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_00:41:46.890.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Melinda Brunstein
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-18 03:32:59	ID requested
⏵ 1	2021-09-09 00:41:49	announced

Schwich OD, Bl, ü, mel N, Keller M, Wegener M, Setty ST, Brunstein ME, Poser I, Mozos IRL, Suess B, M, ü, nch C, McNicoll F, Zarnack K, M, ü, ller-McNicoll M, SRSF3 and SRSF7 modulate 3'UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels. Genome Biol, 22(1):82(2021) [pubmed]

submitter keyword: SRSF3, SRSF7, alternative polyadenylation, CFIm, CPSF5, CPSF6, FIP1, poly(A) site, iCLIP, DaPars, MACE

Christian Münch
contact affiliation	Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
contact email	ch.muench@em.uni-frankfurt.de
lab head
Melinda Brunstein
contact affiliation	Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
contact email	brunstein@med.uni-frankfurt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018090
     1. Label: PRIDE project
     2. Name: SRSF7 and SRSF3 affectSRSF7 and SRSF3 affect 3’UTR length in opposite directions by controlling proximal poly(A)-site usage and CFIm levels 3’UTR length in opposite directions by controlling proximal poly(A)-site usage and CFIm levels