Does base-pairing strength play a role in microRNA repression?

Carmel, Ido; Shomron, Noam; Heifetz, Yael

doi:10.1261/rna.032185.111

Cited by 21 publications

(19 citation statements)

References 63 publications

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“…Temperature may also affect gRNA hybridization, as proposed for microRNAs 100 , in line with temperature-dependent contributions of gRNA GC content and secondary structure ( Supplementary Fig. S27).…”

Section: Crispri Effect Magnitude Depends On Temperature and Phenotypesupporting

confidence: 54%

Gene dosage screens in yeast reveal core signalling pathways controlling heat adaptation

Jann

Johansson²,

Smith

et al. 2020

Preprint

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Heat stress causes proteins to unfold and lose their function, jeopardizing essential cellular processes. To protect against heat and proteotoxic stress, cells mount a dedicated stress-protective programme, the so-called heat shock response (HSR). Our understanding of the mechanisms that regulate the HSR and their contributions to heat resistance and growth is incomplete. Here we employ CRISPRi/a to down- or upregulate protein kinases and transcription factors in S. cerevisiae. We measure gene functions by quantifying perturbation effects on HSR activity, thermotolerance, and cellular fitness at 23, 30 and 38°C. The integration of these phenotypes allowed us to identify core signalling pathways of heat adaptation and reveal novel functions for the high osmolarity glycerol, unfolded protein response and protein kinase A pathways in adjusting both thermotolerance and chaperone expression. We further provide evidence for unknown cross-talk of the HSR with the cell cycle-dependent kinase Cdc28, the primary regulator of cell cycle progression. Finally, we show that CRISPRi efficiency is temperature-dependent and that different phenotypes vary in their sensitivity to knock-down. In summary, our study quantifies regulatory gene functions in different aspects of heat adaptation and advances our understanding of how eukaryotic cells counteract proteotoxic and other heat-caused damage.

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Section: Crispri Effect Magnitude Depends On Temperature and Phenotypesupporting

confidence: 54%

Gene dosage screens in yeast reveal core signalling pathways controlling heat adaptation

Jann

Johansson²,

Smith

et al. 2020

Preprint

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“…The initial motivation for this study was provided by the fact that the thermodynamic properties of the guide-target duplex greatly affect the efficacy of target recognition and silencing ( 15 – 17 ). As previously proposed, slicer-independent unwinding can be viewed as the reverse process of target RNA recognition, with the passenger-strand being regarded as a target of the guide strand ( 2 , 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Slicer-independent mechanism drives small-RNA strand separation during human RISC assembly

Park

Shin

2015

Nucleic Acids Res

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Small RNA silencing is mediated by the effector RNA-induced silencing complex (RISC) that consists of an Argonaute protein (AGOs 1–4 in humans). A fundamental step during RISC assembly involves the separation of two strands of a small RNA duplex, whereby only the guide strand is retained to form the mature RISC, a process not well understood. Despite the widely accepted view that ‘slicer-dependent unwinding’ via passenger-strand cleavage is a prerequisite for the assembly of a highly complementary siRNA into the AGO2-RISC, here we show by careful re-examination that ‘slicer-independent unwinding’ plays a more significant role in human RISC maturation than previously appreciated, not only for a miRNA duplex, but, unexpectedly, for a highly complementary siRNA as well. We discovered that ‘slicer-dependency’ for the unwinding was affected primarily by certain parameters such as temperature and Mg2+. We further validate these observations in non-slicer AGOs (1, 3 and 4) that can be programmed with siRNAs at the physiological temperature of humans, suggesting that slicer-independent mechanism is likely a common feature of human AGOs. Our results now clearly explain why both miRNA and siRNA are found in all four human AGOs, which is in striking contrast to the strict small-RNA sorting system in Drosophila.

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“…3′ compensatory site) to stabilize and supplement the miRNA-target pair. Further influencing low temperature function through binding of the miRNA, analysis of the average GC content in the seed regions of all mature miRNA (available at miRBase.org) among species with varying T b showed that GC content decreases with T b (Carmel et al, 2012). Together, these findings support the hypothesis that there may be adaptations to miRNA binding mechanisms to function at low temperatures, perhaps even altering the mRNAs targeted.…”

Section: Microrna Control Over Cellular Pathways and Processesmentioning

confidence: 70%

Insight into post-transcriptional gene regulation: stress-responsive microRNAs and their role in the environmental stress survival of tolerant animals

Biggar

Storey

2015

Journal of Experimental Biology

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Living animals are constantly faced with various environmental stresses that challenge normal life, including: oxygen limitation, very low or high temperature, as well as restriction of water and food. It has been well established that in response to these stresses, tolerant organisms regularly respond with a distinct suite of cellular modifications that involve transcriptional, translational and posttranslational modification. In recent years, a new mechanism of rapid and reversible transcriptome regulation, via the action of noncoding RNA molecules, has emerged into post-transcriptional regulation and has since been shown to be part of the survival response. However, these RNA-based mechanisms by which tolerant organisms respond to stressed conditions are not well understood. Recent studies have begun to show that non-coding RNAs control gene expression and translation of mRNA to protein, and can also have regulatory influence over major cellular processes. For example, select microRNAs have been shown to have regulatory influence over the cell cycle, apoptosis, signal transduction, muscle atrophy and fatty acid metabolism during periods of environmental stress. As we are on the verge of dissecting the roles of non-coding RNA in environmental stress adaptation, this Commentary summarizes the hallmark alterations in microRNA expression that facilitate stress survival.

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Does base-pairing strength play a role in microRNA repression?

Cited by 21 publications

References 63 publications

Gene dosage screens in yeast reveal core signalling pathways controlling heat adaptation

Gene dosage screens in yeast reveal core signalling pathways controlling heat adaptation

Slicer-independent mechanism drives small-RNA strand separation during human RISC assembly

Insight into post-transcriptional gene regulation: stress-responsive microRNAs and their role in the environmental stress survival of tolerant animals

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