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)
End	86,354,454 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	59,970,961 bp
RNA expression pattern
	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
	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
	79670
	214290
	ENSG00000083223
	ENSMUSG00000035248
	Q5VYS8
	Q5BLK4
	NM_001185059; NM_001185074; NM_024617; NM_001330718
	NM_153538; NM_001373962; NM_001373963; NM_001373964
	NP_001171988; NP_001172003; NP_001317647; NP_078893
	NP_705766; NP_001360891; NP_001360892; NP_001360893
	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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000083223 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000035248 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ "Entrez Gene: ZCCHC6 zinc finger, CCHC domain containing 6".
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.

Structure

Function

References

Further reading