ZCCHC6 explained

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]

Further reading

• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–1795 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . 6 . 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 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . 6 . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–2144 . October 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . 6 . The LIFEdb database in 2006 . Nucleic Acids Research . 34 . Database issue . D415–D418 . January 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .

Notes and References

1. Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O . 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 . 11214970 . 10.1093/dnares/7.6.347 . free .
2. Web site: Entrez Gene: ZCCHC6 zinc finger, CCHC domain containing 6.
3. Rissland OS, Mikulasova A, Norbury CJ . Efficient RNA polyuridylation by noncanonical poly(A) polymerases . Molecular and Cellular Biology . 27 . 10 . 3612–3624 . May 2007 . 17353264 . 1899984 . 10.1128/MCB.02209-06 .
4. Lim J, Ha M, Chang H, Kwon SC, Simanshu DK, Patel DJ, Kim VN . Uridylation by TUT4 and TUT7 marks mRNA for degradation . Cell . 159 . 6 . 1365–1376 . December 2014 . 25480299 . 4720960 . 10.1016/j.cell.2014.10.055 .
5. Heo I, Ha M, Lim J, Yoon MJ, Park JE, Kwon SC, Chang H, Kim VN . 6 . 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 . 23063654 . 10.1016/j.cell.2012.09.022 . free .
6. Thornton JE, Chang HM, Piskounova E, Gregory RI . Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7) . RNA . 18 . 10 . 1875–1885 . October 2012 . 22898984 . 3446710 . 10.1261/rna.034538.112 .
7. Ansari MY, Khan NM, Ahmad N, Green J, Novak K, Haqqi TM . 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 . 30302948 . 10.1002/art.40751 . 6438766 .