Biology:ZCCHC6
 Generic protein structure example |
Terminal uridylyltransferase 7 (TUT7), also known as "zinc finger, CCHC domain containing 6", is an enzyme that in humans is encoded by the ZCCHC6 gene located on chromosome 9.[1][2] The ZCCHC6 protein mediates the terminal uridylation of RNA transcripts with short poly-A tails and is involved in mRNA and microRNA degradation
Structure
The ZCCHC6 gene contains 33 exons with at least six known isoforms due to alternative splicing. The ZCCHC6 gene encodes for a protein that is 171 kDa in molecular weight and is localized to the cytoplasm.
Function
It catalyzes the following reaction, requiring Mg2+ and Mn2+ as co-factors.
UTP + RNA(n) = diphosphate + RNA(n+1) [3]
Uridylation catalyzed by ZCCHC6 takes place readily on deadenylated mRNAs inside the cells.[4] Purified ZZHC6 selectively recognizes and uridylates RNA molecules possessing short poly(A) tails (less than 25 nucleotides) in vitro. In cells depleted of ZCCHC6, the majority of mRNAs lose the signature oligo(U) tails that are characteristic of ZCCHC6 reactivity, and the half-life of mRNA molecules are accordingly prolonged.[4]
In addition to mRNA degradation, uridylation is also thought to function in pre-microRNA maturation, with some group II pre-microRNA requiring 3' mono-uridylation for Dicer processing.[5] ZCCHC6 is thought to work in redundancy with ZCCHC11 to mediate the biogenesis of the let-7 microRNA through uridylation.[6]
Genetic Inactivation of ZCCHC6 Suppresses Interleukin-6 Expression and Reduces the Severity of Experimental Osteoarthritis in Mice.[7]
References
- ↑ "Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research 7 (6): 347–355. December 2000. doi:10.1093/dnares/7.6.347. PMID 11214970.
- ↑ "Entrez Gene: ZCCHC6 zinc finger, CCHC domain containing 6". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=79670.
- ↑ "Efficient RNA polyuridylation by noncanonical poly(A) polymerases". Molecular and Cellular Biology 27 (10): 3612–3624. May 2007. doi:10.1128/MCB.02209-06. PMID 17353264.
- ↑ 4.0 4.1 "Uridylation by TUT4 and TUT7 marks mRNA for degradation". Cell 159 (6): 1365–1376. December 2014. doi:10.1016/j.cell.2014.10.055. PMID 25480299.
- ↑ "Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs". Cell 151 (3): 521–532. October 2012. doi:10.1016/j.cell.2012.09.022. PMID 23063654.
- ↑ "Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)". RNA 18 (10): 1875–1885. October 2012. doi:10.1261/rna.034538.112. PMID 22898984.
- ↑ "Genetic Inactivation of ZCCHC6 Suppresses Interleukin-6 Expression and Reduces the Severity of Experimental Osteoarthritis in Mice". Arthritis & Rheumatology 71 (4): 583–593. April 2019. doi:10.1002/art.40751. PMID 30302948.
Further reading
- "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–1795. November 2000. doi:10.1101/gr.143000. PMID 11076863.
- "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research 11 (3): 422–435. March 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "From ORFeome to biology: a functional genomics pipeline". Genome Research 14 (10B): 2136–2144. October 2004. doi:10.1101/gr.2576704. PMID 15489336.
- "The LIFEdb database in 2006". Nucleic Acids Research 34 (Database issue): D415–D418. January 2006. doi:10.1093/nar/gkj139. PMID 16381901.
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