ZCCHC6

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.[5][6] The ZCCHC6 protein mediates the terminal uridylation of RNA transcripts with short poly-A tails and is involved in mRNA and microRNA degradation

TUT7
Identifiers
Aliases	TUT7, PAPD6, zinc finger CCHC-type containing 6, TENT3B, ZCCHC6, terminal uridylyl transferase 7
External IDs	OMIM: 613467 MGI: 2387179 HomoloGene: 51941 GeneCards: TUT7
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q21.33 Start 86,287,733 bp[1] End 86,354,454 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 B2 Start 59,771,561 bp[2] End 59,823,147 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • nucleotidyltransferase activity • zinc ion binding • metal ion binding • nucleic acid binding • RNA binding • RNA uridylyltransferase activity • GO:0001948 protein binding • miRNA binding • uridylyltransferase activity Cellular component • cytoplasm • nucleoplasm • cytosol Biological process • histone mRNA catabolic process • RNA 3'-end processing • nuclear-transcribed mRNA poly(A) tail shortening • oocyte maturation • negative regulation of transposition, RNA-mediated • miRNA metabolic process • pre-miRNA processing • RNA 3' uridylation • polyuridylation-dependent mRNA catabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79670	214290
Ensembl	ENSG00000083223	ENSMUSG00000035248
UniProt	Q5VYS8	Q5BLK4
RefSeq (mRNA)	NM_001185059 NM_001185074 NM_024617 NM_001330718	NM_153538 NM_001373962 NM_001373963 NM_001373964
RefSeq (protein)	NP_001171988 NP_001172003 NP_001317647 NP_078893	NP_705766 NP_001360891 NP_001360892 NP_001360893
Location (UCSC)	Chr 9: 86.29 – 86.35 Mb	Chr 13: 59.77 – 59.82 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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) [7]

Uridylation catalyzed by ZCCHC6 takes place readily on deadenylated mRNAs inside the cells.[8] 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.[8]

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.[9] ZCCHC6 is thought to work in redundancy with ZCCHC11 to mediate the biogenesis of the let-7 microRNA through uridylation.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000083223 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035248 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O (Dec 2000). "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): 347–55. doi:10.1093/dnares/7.6.347. PMID 11214970.
6. "Entrez Gene: ZCCHC6 zinc finger, CCHC domain containing 6".
7. Rissland OS, Mikulasova A, Norbury CJ (2007). "Efficient RNA polyuridylation by noncanonical poly(A) polymerases". Mol. Cell. Biol. 27 (10): 3612–24. doi:10.1128/MCB.02209-06. PMC 1899984. PMID 17353264.
8. Lim J, Ha M, Chang H, Kwon SC, Simanshu DK, Patel DJ, Kim VN (2014). "Uridylation by TUT4 and TUT7 marks mRNA for degradation". Cell. 159 (6): 1365–76. doi:10.1016/j.cell.2014.10.055. PMC 4720960. PMID 25480299.
9. Heo I, Ha M, Lim J, Yoon MJ, Park JE, Kwon SC, Chang H, Kim VN (2012). "Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs". Cell. 151 (3): 521–32. doi:10.1016/j.cell.2012.09.022. PMID 23063654.
10. Thornton JE, Chang HM, Piskounova E, Gregory RI (2012). "Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)". RNA. 18 (10): 1875–85. doi:10.1261/rna.034538.112. PMC 3446710. PMID 22898984.

Further reading

• Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• 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 (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• 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 (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.