ZCCHC6

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; OMA:TUT7 - orthologs
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 59,919,375 bp [2] End 59,970,961 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tendon of biceps brachii blood buccal mucosa cell periodontal fiber Achilles tendon skin of thigh monocyte epithelium of nasopharynx bone marrow cells oral cavity Top expressed in basilar part of occipital bone granulocyte tibiofemoral joint bone marrow genital tubercle jejunum fetal liver hematopoietic progenitor cell renal corpuscle ileum blood More reference expression data BioGPS 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 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: 59.92 – 59.97 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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 ZCCHC6 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]

Genetic Inactivation of ZCCHC6 Suppresses Interleukin-6 Expression and Reduces the Severity of Experimental Osteoarthritis in Mice. ^[11]

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 (December 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): 347–355. 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 (May 2007). "Efficient RNA polyuridylation by noncanonical poly(A) polymerases". Molecular and Cellular Biology. 27 (10): 3612–3624. 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 (December 2014). "Uridylation by TUT4 and TUT7 marks mRNA for degradation". Cell. 159 (6): 1365–1376. 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, et al. (October 2012). "Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs". Cell. 151 (3): 521–532. doi: 10.1016/j.cell.2012.09.022 . PMID   23063654.
10. Thornton JE, Chang HM, Piskounova E, Gregory RI (October 2012). "Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)". RNA. 18 (10): 1875–1885. doi:10.1261/rna.034538.112. PMC   3446710 . PMID   22898984.
11. Ansari MY, Khan NM, Ahmad N, Green J, Novak K, Haqqi TM (April 2019). "Genetic Inactivation of ZCCHC6 Suppresses Interleukin-6 Expression and Reduces the Severity of Experimental Osteoarthritis in Mice". Arthritis & Rheumatology. 71 (4): 583–593. doi:10.1002/art.40751. PMC   6438766 . PMID   30302948.

Further reading

• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–D418. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.