CPSF6
Domain
Contains an Arg/Ser-rich domain composed of arginine-serine dipeptide repeats within the C-terminal region that is necessary and sufficient for activating mRNA 3'-processing and alternative polyadenylation (APA).
Function
Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:14690600, PubMed:29276085, PubMed:8626397, PubMed:9659921). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:14690600, PubMed:8626397, PubMed:9659921). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream of pA signals and promotes RNA looping, and hence activates directly the mRNA 3'-processing machinery (PubMed:15169763, PubMed:21295486, PubMed:29276085). Plays a role in mRNA export (PubMed:19864460).
(Microbial infection) Binds HIV-1 capsid-nucleocapsid (HIV-1 CA-NC) complexes and might thereby promote the integration of the virus in the nucleus of dividing cells (in vitro).
Post-translational modifications
Phosphorylated (PubMed:29276085). Phosphorylated in the Arg/Ser-rich domain by SRPK1, in vitro (PubMed:29276085).
Symmetrically dimethylated on arginine residues in the GAR motif by PRMT5 in a WDR77- and CLNS1A-dependent manner (PubMed:20562214). Asymmetrically dimethylated on arginine residues in the GAR motif by PRMT1 (PubMed:20562214).
Sequence Similarities
Belongs to the RRM CPSF6/7 family.
Cellular localization
- Nucleus
- Nucleus
- Nucleoplasm
- Nucleus speckle
- Cytoplasm
- Shuttles between the nucleus and the cytoplasm in a transcription- and XPO1/CRM1-independent manner, most probably in complex with the cleavage factor Im complex (CFIm) (PubMed:19864460). Colocalizes with PSPC1 in punctate subnuclear structures often located adjacent to nuclear speckles, called paraspeckles, and corresponding to interchromatin granules-associated zones (IGAZs) (PubMed:17267687). Distribution in speckles and paraspeckles varies during the cell cycle (PubMed:17267687). Associates at sites of active transcription on nascent perichromatin fibrils (PFs) and perichromatin granules (PubMed:17267687). Nuclear import is mediated via interaction with TNPO3 independently of CPSF6 phosphorylation status (PubMed:30916345).
Alternative names
CFIM68, CPSF6, Cleavage and polyadenylation specificity factor subunit 6, Cleavage and polyadenylation specificity factor 68 kDa subunit, Cleavage factor Im complex 68 kDa subunit, Pre-mRNA cleavage factor Im 68 kDa subunit, Protein HPBRII-4/7, CPSF 68 kDa subunit, CFIm68