PMID- 29844106
OWN - NLM
STAT- MEDLINE
DCOM- 20180808
LR  - 20220410
IS  - 1469-9001 (Electronic)
IS  - 1355-8382 (Print)
IS  - 1355-8382 (Linking)
VI  - 24
IP  - 8
DP  - 2018 Aug
TI  - tRNA fragments (tRFs) guide Ago to regulate gene expression 
      post-transcriptionally in a Dicer-independent manner.
PG  - 1093-1105
LID - 10.1261/rna.066126.118 [doi]
AB  - 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.
CI  - (c) 2018 Kuscu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA 
      Society.
FAU - Kuscu, Canan
AU  - Kuscu C
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia 22901, USA.
FAU - Kumar, Pankaj
AU  - Kumar P
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia 22901, USA.
FAU - Kiran, Manjari
AU  - Kiran M
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia 22901, USA.
FAU - Su, Zhangli
AU  - Su Z
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia 22901, USA.
FAU - Malik, Asrar
AU  - Malik A
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia 22901, USA.
FAU - Dutta, Anindya
AU  - Dutta A
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia 22901, USA.
LA  - eng
GR  - P01 CA104106/CA/NCI NIH HHS/United States
GR  - R01 GM084465/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180529
PL  - United States
TA  - RNA
JT  - RNA (New York, N.Y.)
JID - 9509184
RN  - 0 (AGO1 protein, human)
RN  - 0 (AGO2 protein, human)
RN  - 0 (AGO3 protein, human)
RN  - 0 (Argonaute Proteins)
RN  - 0 (Autoantigens)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (TNRC6A protein, human)
RN  - 9014-25-9 (RNA, Transfer)
RN  - EC 3.1.26.3 (DICER1 protein, human)
RN  - EC 3.1.26.3 (DROSHA protein, human)
RN  - EC 3.1.26.3 (Ribonuclease III)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Argonaute Proteins/*genetics
MH  - Autoantigens/*metabolism
MH  - Cell Line
MH  - DEAD-box RNA Helicases/*genetics
MH  - Eukaryotic Initiation Factors/*genetics
MH  - Gene Expression Regulation/*genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Protein Processing, Post-Translational/genetics
MH  - RNA Interference
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/genetics
MH  - RNA, Transfer/*genetics
MH  - RNA-Binding Proteins/*metabolism
MH  - Ribonuclease III/*genetics
PMC - PMC6049499
OTO - NOTNLM
OT  - post-transcriptional gene regulation
OT  - small noncoding RNA
OT  - tRF
OT  - tRNA fragments
EDAT- 2018/05/31 06:00
MHDA- 2018/08/09 06:00
PMCR- 2019/08/01
CRDT- 2018/05/31 06:00
PHST- 2018/02/08 00:00 [received]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2018/08/09 06:00 [medline]
PHST- 2018/05/31 06:00 [entrez]
PHST- 2019/08/01 00:00 [pmc-release]
AID - rna.066126.118 [pii]
AID - RA [pii]
AID - 10.1261/rna.066126.118 [doi]
PST - ppublish
SO  - RNA. 2018 Aug;24(8):1093-1105. doi: 10.1261/rna.066126.118. Epub 2018 May 29.