tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 29, 2018
- Source ID
- 10.1261/rna.066126.118
Entities
People
- Anindya Dutta
- Asrar B Malik
- Canan Kuscu
- Manjari Kiran
- Pankaj Kumar
- Zhangli Su
Organizations
- National Institutes of Health
- United States Department of Defense