CPSF6

The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. The cleavage factor complex is composed of four polypeptides. This gene encodes the 68kD subunit. It has a domain organization reminiscent of spliceosomal proteins. [provided by RefSeq]

Full Name

cleavage and polyadenylation specific factor 6, 68kDa

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:9659921, PubMed:8626397, PubMed:14690600, PubMed:29276085).

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:9659921, PubMed:8626397, PubMed:14690600).

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:29276085, PubMed:21295486).

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).

Biological Process

Messenger ribonucleoprotein complex assembly Source: UniProtKB
mRNA alternative polyadenylation Source: UniProtKB
mRNA processing Source: UniProtKB
Positive regulation of RNA export from nucleus Source: UniProtKB
Pre-mRNA cleavage required for polyadenylation Source: UniProtKB
Protein heterotetramerization Source: UniProtKB
Protein tetramerization Source: UniProtKB

Cellular Location

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).

PTM

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).