NUDT21
Description
The NUDT21 (nudix hydrolase 21) is a protein-coding gene located on chromosome 16.
Cleavage and polyadenylation specificity factor subunit 5 (CPSF5) is an enzyme that in humans is encoded by the NUDT21 gene. It belongs to the Nudix family of hydrolases. The protein encoded by this gene is one subunit of the cleavage factor Im complex 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. This gene encodes the 25kD subunit of the protein complex, which is composed of four polypeptides.
NUDT21 is a component of the cleavage factor Im (CFIm) complex, which plays a crucial role in the maturation of pre-mRNA into functional mRNAs. This complex functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing, a process necessary for the formation of mature mRNAs. CFIm recruits multiprotein complexes to specific sequences on the pre-mRNA 3'-end, known as cleavage and polyadenylation signals (pA signals). Many pre-mRNAs contain multiple pA signals, leading to alternative cleavage and polyadenylation (APA), which produces mRNAs with varying 3'-end structures. CFIm acts as a key regulator in this process, controlling the selection of cleavage and polyadenylation sites during APA by binding to 5'-UGUA-3' elements located in the 3'-untranslated region (UTR) of numerous pre-mRNAs. NUDT21/CPSF5 indirectly activates the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7. NUDT21 binds to 5'-UGUA-3' elements situated upstream of pA signals, which function as enhancers of pre-mRNA 3'-end processing. The homodimer of NUDT21 can simultaneously recognize two 5'-UGUA-3' elements within the pre-mRNA. NUDT21 plays a role in somatic cell fate transitions and pluripotency by regulating widespread alterations in gene expression through APA-dependent functions. NUDT21 also binds to chromatin and interacts with various proteins, including CPSF6, CPSF7, FIP1L1, PABPN1, PAPOLA, SNRNP70, and VIRMA. It can bind to but does not hydrolyze mono- and di-adenosine nucleotides.
NUDT21 is also known as CFIM25, CPSF5.