Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation.

By S. Bagga, J. Bracht, Shaun E. Hunter, K. Massirer, J. Holtz, Rachel Eachus, A. Pasquinelli. Cell, 2005

1,431 citations recorded by the source corpus.

MicroRNAs (miRNAs) are approximately 22 nucleotide RNAs that negatively regulate the expression of protein-coding genes. In a present model of miRNA function in animals, miRNAs that form imperfect duplexes with their targets inhibit protein expression without affecting mRNA levels. Here, we report that in C. elegans, regulation by the let-7 miRNA results in degradation of its lin-41 target mRNA, despite the fact that its 3'UTR regulatory sequences can only partially base-pair with the miRNA. Furthermore, lin-14 and lin-28 are targets of the lin-4 miRNA, and we show that the mRNA levels for these protein-coding genes significantly decrease in response to lin-4 expression. This study reveals that mRNAs containing partial miRNA complementary sites can be targeted for degradation in vivo, raising the possibility that regulation at the level of mRNA stability may be more common than previously appreciated for the miRNA pathway.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d717bbf9b1d525693d7ad6e2b02db443a0fc3441

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Citations in the corpus

Regulation of the p27Kip1 tumor suppressor by miR‐221 and miR‐222 promotes cancer cell proliferation (2007, background): “…(30UTR) of protein coding genes and subsequent induction of translation inhibi- tion, which can also be associated with transcript destabiliza- tion (Bagga et al, 2005; Giraldez et al, 2006; Wu et al, 2006). miRNAs have been found to be implicated in a large variety of cellular processes, and…”
The let-7 microRNA represses cell proliferation pathways in human cells. (2007, background): “let-7 seems to regulate its target genes primarily at the level of translation (18, 29); however, recent evidence indicates that let-7 can also cause the instability of its target mRNAs (11, 15).”
Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. (2009, background): “Though P-body integrity (as judged by light microscopy) is not essential for miRNA function [70,71 ], many of the P-body components were shown to play an important role in miRNA-mediated repression [10–12,53,62,70,72].”
Illuminating the silence: understanding the structure and function of small RNAs (2007, background): “Recently, miRNAs have been shown to enhance mRNA degradatio”
Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. (2006, background): “While degradation of imperfectly matched targets may not involve slicer activity (Bagga et al. 2005), our findings suggest a model for their recognition similar to that of Brown et al. 29-O-Methyl modification of siRNAs does not detectably affect silencing of perfectly matched targets, arguing that…”
Functions of microRNAs and related small RNAs in plants (2006, background): “This repression can be accompanied by mRNA decay through a slicer-independent mechanis”
Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. (2006, background): “This portion of the guide strand is analogous to the ‘‘seed’’ region at the 59 end of a microRNA that is implicated in gene regulation by inhibition of translation and/or mRNA degradation (Lai 2002; Lewis et al. 2003; Stark et al. 2003; Yekta et al. 2004; Bagga et al. 2005).”
Mechanisms of miRNA-Mediated Gene Regulation from Common Downregulation to mRNA-Specific Upregulation (2014, background): “Alternatively, sequence-specific endonucleolytic mRNA cleavage by polysomal ribonuclease 1 (PMR1) may occur in parallel [70] (Figure 1(a)).”
Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. (2005, positive): “However, recent data show that animal miRNAs can also destabilize target mRNAs ( Bagga et al., 2005; Lim etal., 2005),suggesting thatmiRNAs could shape transcript patterns.”