tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner

被引：271

作者：

Kuscu, Canan ^{[1
]}

Kumar, Pankaj ^{[1
]}

Kiran, Manjari ^{[1
]}

Su, Zhangli ^{[1
]}

Malik, Asrar ^{[1
]}

Dutta, Anindya ^{[1
]}

机构：

[1] Univ Virginia, Dept Biochem & Mol Genet, Sch Med, Charlottesville, VA 22901 USA

来源：

RNA | 2018年 / 24卷 / 08期

基金：

美国国家卫生研究院;

关键词：

tRNA fragments; tRF; post-transcriptional gene regulation; small noncoding RNA; RIBOSOMAL DNA; BIOGENESIS; REVEALS; ARGONAUTE; MICRORNAS; IDENTIFICATION; AMPLIFICATION; TRANSCRIPTION; DETERMINANTS; MECHANISMS;

D O I：

10.1261/rna.066126.118

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-3mediated 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 posttranscriptionally through an Argonaute-GW182 containing RISC via sequence matches with target mRNAs.

引用

页码：1093 / 1105

页数：13

共 5 条

[1] tRNA-derived fragments (tRFs) regulate post-transcriptional gene expression via AGO-dependent mechanism in IL-1β stimulated chondrocytes
Green, J. A.
Ansari, M. Y.
Ball, H. C.
Haqqi, T. M.
OSTEOARTHRITIS AND CARTILAGE, 2020, 28 (08) : 1102 - 1110
[2] LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes
Zhu, Li
Kandasamy, Suresh K.
Liao, Susan E.
Fukunaga, Ryuya
NATURE COMMUNICATIONS, 2018, 9
[3] LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes
Li Zhu
Suresh K. Kandasamy
Susan E. Liao
Ryuya Fukunaga
Nature Communications, 9
[4] Author Correction: LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes
Li Zhu
Suresh K. Kandasamy
Susan E. Liao
Ryuya Fukunaga
Nature Communications, 10
[5] LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes (vol 9, 4031, 2018)
Zhu, Li
Kandasamy, Suresh K.
Liao, Susan E.
Fukunaga, Ryuya
NATURE COMMUNICATIONS, 2019, 10 (1)

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