ZCCHC6

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (mRNA)

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RefSeq (protein)

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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 chromosone 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 polyA-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]

References

  1. 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.
  2. "Entrez Gene: ZCCHC6 zinc finger, CCHC domain containing 6".
  3. 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.
  4. 4.0 4.1 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.
  5. 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.
  6. 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