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Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments

Authors
 Hee Cho  ;  Wooseong Lee  ;  Geon-Woo Kim  ;  Seung-Hoon Lee  ;  Jae-Su Moon  ;  Minwoo Kim  ;  Hyun Seok Kim  ;  Jong-Won Oh 
Citation
 NUCLEIC ACIDS RESEARCH, Vol.47(18) : 9888-9901, 2019 
Journal Title
NUCLEIC ACIDS RESEARCH
ISSN
 0305-1048 
Issue Date
2019
MeSH
Cell Line, Tumor ; Cell Proliferation/genetics* ; Cytoplasm/genetics* ; Gene Expression Regulation, Viral/genetics ; Humans ; Molecular Chaperones/genetics ; RNA Precursors/genetics* ; RNA, Transfer/genetics*
Abstract
tRNA-derived RNA fragments (tRFs) have emerged as a new class of functional RNAs implicated in cancer, metabolic and neurological disorders, and viral infection. Yet our understanding of their biogenesis and functions remains limited. In the present study, through analysis of small RNA profile we have identified a distinct set of tRFs derived from pre-tRNA 3' trailers in the hepatocellular carcinoma cell line Huh7. Among those tRFs, tRF_U3_1, which is a 19-nucleotide-long chr10.tRNA2-Ser(TGA)-derived trailer, was expressed most abundantly in both Huh7 and cancerous liver tissues, being present primarily in the cytoplasm. We show that genetic loss of tRF_U3_1 does not affect cell growth and it is not involved in Ago2-mediated gene silencing. Using La/SSB knockout Huh7 cell lines, we demonstrate that this nuclear-cytoplasmic shuttling protein directly binds to the 3' U-tail of tRF_U3_1 and other abundantly expressed trailers and plays a critical role in their stable cytoplasmic accumulation. The pre-tRNA trailer-derived tRFs capable of sequestering the limiting amounts of La/SSB in the cytoplasm rendered cells resistant to various RNA viruses, which usurp La/SSB with RNA chaperone activity for their gene expression. Collectively, our results establish the trailer-derived tRF-La/SSB interface, regulating viral gene expression.
Files in This Item:
T201903864.pdf Download
DOI
10.1093/nar/gkz732
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Seok(김현석) ORCID logo https://orcid.org/0000-0003-4498-8690
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173070
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