TRBP alters human precursor microRNA processing in vitro
Abstract
MicroRNAs play central roles in controlling gene expression in human cells. Sequencing data show that many miRNAs are produced at different levels and as multiple isoforms that can vary in length at their 5′ or 3′ ends, but the biogenesis and functional significance of these RNAs are largely unknown. We show here that the human trans -activation response (TAR) RNA binding protein (TRBP), a known molecular partner of the miRNA processing enzyme Dicer, changes the rates of pre-miRNA cleavage in an RNA-structure-specific manner. Furthermore, TRBP can trigger the generation of iso-miRNAs (isomiRs) that are longer than the canonical sequence by one nucleotide. We show that this change in miRNA processing site can alter guide strand selection, resulting in preferential silencing of a different mRNA target. These results implicate TRBP as a key regulator of miRNA processing and targeting in humans.
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Changes in Dicer processing sites produce isomiRs with altered thermodynamic end stabilities that reverse strand selection of mammalian miRNAs in vitro.
“Indeed, changes in Dicer processing sites produce isomiRs with altered thermodynamic end stabilities that reverse strand selection of mammalian miRNAs in vitro (Kim et al., 2014; Lee & Doudna, 2012; Wilson & Doudna, 2014; Figure 4d).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Lee & Doudna, 2012
The isomiR-production section reports that Dicer–TRBP shifts the pre-miR-200a cleavage site, producing longer isomiRs in vitro. The functional-effects section links the altered products to end stability and guide-strand selection, but reports a change from strong 3p preference to similar use of both strands—not a reversal. Strand activity was tested with a reporter assay in human cells, rather than in vitro. (LLM, conf=0.89)
Experimental — accuracy not yet measuredThese variations can also influence the relative TS of miRNA duplex ends.
“In addition, these variations can also influence the relative TS of miRNA duplex ends (Lee & Doudna, 2012; Starega‐Roslan, Koscianska, Kozlowski, & Krzyzosiak, 2011).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Lee & Doudna, 2012
IsomiRs resulting from altered Dicer processing sites have been shown to change the thermodynamic properties of mammalian miRNAs, leading to reversed strand selection.
“Indeed, isomiRs resulting from altered Dicer processing sites have been shown to change the thermodynamic properties of mammalian miRNAs, leading to reversed strand selection (Lee & Doudna, 2012; Wilson & Doudna, 2014).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Lee & Doudna, 2012
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Research works printed but not linked: 1
- Forstemann K, Tomari Y, Du T, Vagin VV, Denli AM, Bratu DP, Klattenhoff C, Theurkauf WE, Zamore PD. 2005. Normal microRNA maturation and germ-line stem cell maintenance requires Loqua- cious, a double-stranded RNA-binding domain protein. PLoS Biol 3: e236. doi: 10.1371/journal.pbio.0030236. · DOI
Cited by
Sorted by citations
Regulation of microRNA biogenesis
Ha, M., & Kim, V. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3838 · Cited by 5,462 · see citing works
microRNA strand selection: Unwinding the rules
Medley, J. C., Panzade, G., & Zinovyeva, A. Y. (2021) · WIREs RNA · doi:10.1002/wrna.1627 · Cited by 225 · see citing works
Abe, M., Naqvi, A., Hendriks, G.-J., Feltzin, V., Zhu, Y., Grigoriev, A., & Bonini, N. M. (2014) · Genes & Development · doi:10.1101/gad.226654.113 · Cited by 68 · see citing works
- Authors
- Lee, H. Y., & Doudna, J. A.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-09-24
- Volume
- 18
- Issue
- 11
- Pages
- 2012-2019
- ISSN
- 1355-8382
- 1469-9001
- Cited by
- 152
- References
- 0
- Language
- en
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