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PARN and TOE1 constitute a 3 ' end maturation module for nuclear non-coding RNAs

Cited 28 time in Web of Science Cited 27 time in Scopus
Authors
Son, Ahyeon; Park, Jong-Eun; Kim, V. Narry
Issue Date
2018-04
Citation
Cell Reports, Vol.23 No.3, pp.888-898
Abstract
Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs). scaRNAs are strongly downregulated when PARN and TOE1 are compromised together, leading to defects in small nuclear RNA (snRNA) pseudouridylation. They also function redundantly in the biogenesis of telomerase RNA component (TERC), which shares sequence motifs found in H/ACA box scaRNAs. Our findings extend the knowledge of nuclear ncRNA biogenesis, and they provide insights into the pathology of PARN/TOE1-associated genetic disorders whose therapeutic treatments are currently unavailable.
ISSN
2211-1247
URI
https://hdl.handle.net/10371/171872
DOI
https://doi.org/10.1016/j.celrep.2018.03.089
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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