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tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner.
RNA. 2018 08; 24(8):1093-1105.RNA

Abstract

tRNA related RNA fragments (tRFs), also known as tRNA-derived RNAs (tdRNAs), are abundant small RNAs reported to be associated with Argonaute proteins, yet their function is unclear. We show that endogenous 18 nucleotide tRFs derived from the 3' ends of tRNAs (tRF-3) post-transcriptionally repress genes in HEK293T cells in culture. tRF-3 levels increase upon parental tRNA overexpression. This represses target genes with a sequence complementary to the tRF-3 in the 3' UTR. The tRF-3-mediated repression is Dicer-independent, Argonaute-dependent, and the targets are recognized by sequence complementarity. Furthermore, tRF-3:target mRNA pairs in the RNA induced silencing complex associate with GW182 proteins, known to repress translation and promote the degradation of target mRNAs. RNA-seq demonstrates that endogenous target genes are specifically decreased upon tRF-3 induction. Therefore, Dicer-independent tRF-3s, generated upon tRNA overexpression, repress genes post-transcriptionally through an Argonaute-GW182 containing RISC via sequence matches with target mRNAs.

Authors+Show Affiliations

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

29844106

Citation

Kuscu, Canan, et al. "TRNA Fragments (tRFs) Guide Ago to Regulate Gene Expression Post-transcriptionally in a Dicer-independent Manner." RNA (New York, N.Y.), vol. 24, no. 8, 2018, pp. 1093-1105.
Kuscu C, Kumar P, Kiran M, et al. TRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA. 2018;24(8):1093-1105.
Kuscu, C., Kumar, P., Kiran, M., Su, Z., Malik, A., & Dutta, A. (2018). TRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA (New York, N.Y.), 24(8), 1093-1105. https://doi.org/10.1261/rna.066126.118
Kuscu C, et al. TRNA Fragments (tRFs) Guide Ago to Regulate Gene Expression Post-transcriptionally in a Dicer-independent Manner. RNA. 2018;24(8):1093-1105. PubMed PMID: 29844106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. AU - Kuscu,Canan, AU - Kumar,Pankaj, AU - Kiran,Manjari, AU - Su,Zhangli, AU - Malik,Asrar, AU - Dutta,Anindya, Y1 - 2018/05/29/ PY - 2018/02/08/received PY - 2018/05/24/accepted PY - 2018/5/31/pubmed PY - 2018/8/9/medline PY - 2018/5/31/entrez KW - post-transcriptional gene regulation KW - small noncoding RNA KW - tRF KW - tRNA fragments SP - 1093 EP - 1105 JF - RNA (New York, N.Y.) JO - RNA VL - 24 IS - 8 N2 - tRNA related RNA fragments (tRFs), also known as tRNA-derived RNAs (tdRNAs), are abundant small RNAs reported to be associated with Argonaute proteins, yet their function is unclear. We show that endogenous 18 nucleotide tRFs derived from the 3' ends of tRNAs (tRF-3) post-transcriptionally repress genes in HEK293T cells in culture. tRF-3 levels increase upon parental tRNA overexpression. This represses target genes with a sequence complementary to the tRF-3 in the 3' UTR. The tRF-3-mediated repression is Dicer-independent, Argonaute-dependent, and the targets are recognized by sequence complementarity. Furthermore, tRF-3:target mRNA pairs in the RNA induced silencing complex associate with GW182 proteins, known to repress translation and promote the degradation of target mRNAs. RNA-seq demonstrates that endogenous target genes are specifically decreased upon tRF-3 induction. Therefore, Dicer-independent tRF-3s, generated upon tRNA overexpression, repress genes post-transcriptionally through an Argonaute-GW182 containing RISC via sequence matches with target mRNAs. SN - 1469-9001 UR - https://www.unboundmedicine.com/medline/citation/29844106/tRNA_fragments__tRFs__guide_Ago_to_regulate_gene_expression_post_transcriptionally_in_a_Dicer_independent_manner_ L2 - http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=29844106 DB - PRIME DP - Unbound Medicine ER -