miRNA targeting and alternative splicing in the stress response – events hosted by membrane-less compartments

Abstract

Stress can be temporary or chronic, and mild or acute. Depending on its extent and severity, cells either alter their metabolism, and adopt a new state, or die. Fluctuations in environmental conditions occur frequently, and such stress disturbs cellular homeostasis, but in general, stresses are reversible and last only a short time. There is increasing evidence that regulation of gene expression in response to temporal stress happens post-transcriptionally in specialized subcellular membrane-less compartments called ribonucleoprotein (RNP) granules. RNP granules assemble through a concentrationdependent liquid-liquid phase separation of RNA-binding proteins that contain low-complexity sequence domains (LCDs). Interestingly, many factors that regulate microRNA (miRNA) biogenesis and alternative splicing are RNA-binding proteins that contain LCDs and localize to stress-induced liquid-like compartments. Consequently, gene silencing through miRNAs and alternative splicing of premRNAs are emerging as crucial post-transcriptional mechanisms that function on a genome-wide scale to regulate the cellular stress response. In this Review, we describe the interplay between these two post-transcriptional processes that occur in liquid-like compartments as an adaptive cellular response to stress.

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

“…A single miRNA could regulate many target genes at a time, and a single target mRNA could also be regulated by several miRNAs (Chowdhury et al, 2014;O'Brien et al, 2018), therefore implying the existence of the coordinated miRNA network in regulating the gene expression. Moreover, numerous evidence showing that the miRNA expression, regulatory action, and localization can change due to cellular environments (Ebert and Sharp, 2012;Kucherenko and Shcherbata, 2018). Serum starvation in multiple human cell lines has demonstrated that a significant decrease in intracellular miRNA levels with higher extracellular releases of these miRNAs either in vesicle form or as in circulating free miRNAs (Wang et al, 2010).…”

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells

“…MicroRNAs (miRNAs) have been reported to be implicated in many cell functions, such as proliferation, differentiation, development, and apoptosis . miRNAs are differentially expressed during the course of liver fibrosis.…”

Morphine modulates the expression of mu‐opioid receptor exon 5‐associated full‐length C‐terminal splice variants by upregulating miR‐378a‐3p

“…There are several possibilities. First, miRNA regulation and alternative splicing are two independent but closely related post‐transcriptional processes . miRNAs can directly target some alternative splicing factors, leading to changes in the alternative splicing profile.…”

“…First, miRNA regulation and alternative splicing are two independent but closely related post-transcriptional processes. 32 miRNAs can directly target some alternative splicing factors, leading to changes in the alternative splicing profile. It will be interesting to further investigate whether miR-378a-3p can alter the expression of the alternative splicing factors that can control splicing for specific MOR-1Bs.…”