Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish

By A. Bazzini, Miler T. Lee, Antonio J. Giráldez. Science, 2012

730 citations recorded by the source corpus.

Translation Block MicroRNAs (miRNAs) are small, noncoding RNA genes that are found in the genomes of most eukaryotes, where they play an important role in the regulation of gene expression. Although whether gene activity is repressed by blocking translation of messenger RNA (mRNA) targets, or by promoting their deadenylation and then degradation, has been open to debate. Bazzini et al. (p. 233, published online 15 March) and Djuranovic et al. (p. 237) looked at early points in the repression reaction in the zebrafish embryo or in Drosophila tissue culture cells, respectively, and found that translation was blocked before target mRNAs were significantly deadenylated and degraded. Thus, miRNAs appear to interfere with the initiation step of translation. MicroRNAs act to repress their messenger RNA targets first by blocking translation initiation and then through degradation. MicroRNAs regulate gene expression through deadenylation, repression, and messenger RNA (mRNA) decay. However, the contribution of each mechanism in non-steady-state situations remains unclear. We monitored the impact of miR-430 on ribosome occupancy of endogenous mRNAs in wild-type and dicer mutant zebrafish embryos and found that miR-430 reduces the number of ribosomes on target mRNAs before causing mRNA decay. Translational repression occurs before complete deadenylation, and disrupting deadenylation with use of an internal polyadenylate tail did not block target repression. Lastly, we observed that ribosome density along the length of the message remains constant, suggesting that translational repression occurs by reducing the rate of initiation rather than affecting elongation or causing ribosomal drop-off. These results show that miR-430 regulates translation initiation before inducing mRNA decay during zebrafish development.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/88b713fc0872a9d91f488f9e9231990c7b782c7f

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

In Molecular Biology

Citations in the corpus

Predicting effective microRNA target sites in mammalian mRNAs (2015, methodology): “…ID, or data source Reference Figure 1A, Figure 1—figure supplement 4A GSM854425, GSM854430, GSM854431, GSM854436, GSM854437, GSM854442, GSM854443 (Bazzini et al., 2012) Figure 1B, Figure 6B GSM1012118, GSM1012119, GSM1012120, GSM1012121, GSM1012122, GSM1012123 (Loeb et al., 2012) Figure 1C,…”
Biogenesis, Turnover, and Mode of Action of Plant MicroRNAs[OPEN] (2013, background): “In animals, kinetic analysis has demonstrated that translational repression precedes mRNA deadenylation and destabilization (Fabian et al., 2009; Bazzini et al., 2012; Béthune et al., 2012; Djuranovic et al., 2012) and may be required for mRNA destabilization (Meijer et al.”
Codon identity regulates mRNA stability and translation efficiency during the maternal‐to‐zygotic transition (2016, positive): “The poly(A) tail length of injected mRNA was visualized with a modified version of the high-resolution poly(A) tail assay (Hire PAT) (Bazzini et al, 2012).”
The Functions of MicroRNAs: mRNA Decay and Translational Repression. (2015, background): “By monitoring the impact of miR-430 on ribosome occupancy of endogenous mRNAs, it was found that miR-430 reduces the number of ribosomes on target mRNAs in early embryos at 4 hpf before the completion of deadenylation and mRNA decay, supporting the model that miRNAs induce translational repression b”
Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation (2014, methodology): “Recent studies have used ribosome foot-printing (Ingolia et al , 2009; Bazzini et al , 2012) to characterize the coding potential of different transcripts (Chew et al , 2013; Guttman et al , 2013) and identify translated protein-coding sequences (Ingolia et al , 2011; Brar et al , 2012; Michel et…”
MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions (2016, background): “[29] found that miR-430 reduces the number of ribosomes on target mRNAs in wild type and Dicer mutant zebrafish embryos indicating that miRNAs can regulate translation at an initiation step.”
m6A-dependent regulation of messenger RNA stability (2013, neutral): “To dissect the role of YTHDF2 we employed ribosome profiling to assess the ribosome loading of each mRNA represented as ribosome-protected reads 21,22 .”
Poly(A)-tail profiling reveals an embryonic switch in translational control (2014, neutral): “Global measurements indicate that miRNA targeting causes mostly mRNA destabilization, with translational repression comprising a detectable but minor component of the overall repression 33–36 .”