Mammalian microRNAs predominantly act to decrease target mRNA levels
By Huili Guo, Nicholas T. Ingolia, Jonathan S. Weissman, David P. Bartel. Nature, 2010
4,048 citations recorded by the source corpus.
MicroRNAs (miRNAs) are endogenous ∼22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/b01974fd8c6c8ffc92fe1e4b8eb27806cdc6181f
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
- David P. Bartel
- Phillip A. Sharp
- Nikolaus Rajewsky
- Margaret S. Ebert
- Yukihide Tomari
- Igor Ulitsky
- Jin-Wu Nam
- Thomas Tuschl
In Molecular Biology
- David P. Bartel
- Phillip A. Sharp
- Yukihide Tomari
- Thomas Tuschl
- A. Pasquinelli
- Debashish Chowdhury
- John S. Mattick
- Nikolaus Rajewsky
Citations in the corpus
- Conserved Function of lincRNAs in Vertebrate Embryonic Development Despite Rapid Sequence Evolution (2011, methodology): “Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation.”
- Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3' UTRs and Near Stop Codons (2012, neutral): “Although miRNAs can inhibit their target mRNAs by promoting either transcript degradation or translational repression (Guo et al., 2010; Hendrickson et al., 2009), the factors that determine which fate predominates are not well understood.”
- Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp™ (2014, background): “MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that regulate gene expression at the levels of mRNA stability and translation (Pillai et al., 2005; Eulalio et al., 2008; Guo et al., 2010).”
- Current prospects for RNA interference-based therapies (2011, background): “Interestingly, some miRNA-mediated translational repression is reversible 21 .”
- MicroRNA regulation by RNA-binding proteins and its implications for cancer (2011, background): “Remarkably, in mammalian cells, observed changes in ribosome occupancy on miRNA targeting largely reflect concurrent mRNA destabilization, rather than persistence of repressed mRNA”
- Poly(A)-tail profiling reveals an embryonic switch in translational control (2014, positive): “We conclude that when poly(A)-tail length is uncoupled from TE, the translational repression often detected as a minor component of the overall repression 33–35 arises from a mechanism different from the one that dominates pre-gastrulation.”
- Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs (2013, methodology): “The maximum 30 bp window ratio of HeLa ribosomal/RNA-seq reads [22] is plotted for exons of lincRNAs, 39 UTRs and coding sequences (CDS).”
- Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization (2011, background): “Genomic and proteomic identification of miR-200 targets Recent studies suggest that in mammalian cells, miRNAs regulate most of their direct targets at both mRNA and protein level”
- Molecular aspects of the pathogenesis of periodontitis. (2015, background): “The (microRNA/ microRNA) -complex is loaded on the Argonaute 2 protein during assembly of the microRNA-induced silencing complex, which shuts down target mRNAs (26).”
- The rise of regulatory RNA (2014, background): “81,82 .”
- Roles for microRNAs in conferring robustness to biological processes. (2012, positive): “More precisely, because translational repression typically accounts for only 20% of miRNA-mediated repression (Guo et al., 2010), the dominant effect is the reduction of a gene’s overall translation events by reducing the lifetime of the target mRNA in the cytoplasm.”