microRNAs (miRNAs) play a central role in the regulation of gene expression by targeting specific mRNAs for degradation or translational repression. Each miRNA is post‐transcriptionally processed into a duplex comprising two strands. One of the two miRNA strands is selectively loaded into an Argonaute protein to form the miRNA‐Induced Silencing Complex (miRISC) in a process referred to as miRNA strand selection. The other strand is ejected from the complex and is subject to degradation. The target gene specificity of miRISC is determined by sequence complementarity between the Argonaute‐loaded miRNA strand and target mRNA. Each strand of the miRNA duplex has the capacity to be loaded into miRISC and possesses a unique seed sequence. Therefore, miRNA strand selection plays a defining role in dictating the specificity of miRISC toward its targets and provides a mechanism to alter gene expression in a switch‐like fashion. Aberrant strand selection can lead to altered gene regulation by miRISC and is observed in several human diseases including cancer. Previous and emerging data shape the rules governing miRNA strand selection and shed light on how these rules can be circumvented in various physiological and pathological contexts. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs
Post ENCODE, regulatory sRNAs (rsRNAs) like miRNAs have established their status as one of the core regulatory elements of cell systems. However, large number of rsRNAs are compromised due to traditional approaches to identify miRNAs, limiting the otherwise vast world of rsRNAs mainly to hair-pin loop bred typical miRNAs. The present study has analyzed for the first time a huge volume of sequencing data from 4997 individuals and 25 cancer types to report 11 234 potentially regulatory small RNAs which appear to have deep reaching impact. The rsRNA-target interactions have been studied and validated extensively using experimental data from AGO-crosslinking, DGCR8 knockdown, CLASH, proteome and expression data. A subset of such interactions was also validated independently in the present study using multiple cell lines, by qPCR. Several of the potential rsRNAs have emerged as a critical cancer biomarker controlling some important spots of cell system. The entire study has been presented into an interactive info-analysis portal handling more than 260 GB of processed data. The possible degree of cell system regulation by sRNAs appears to be much higher than previously assumed.
Idiopathic Pulmonary Fibrosis (IPF) is an incurable progressive fibrotic disease of the lungs. We currently lack a systematic understanding of IPF biology and a systems approach may offer new therapeutic insights. Here, for the first time, a large volume of high throughput genomics data has been unified to derive the most common molecular signatures of IPF. A set of 39 differentially expressed genes (DEGs) was found critical to distinguish IPF. Using high confidence evidences and experimental data, system level networks for IPF were reconstructed, involving 737 DEGs found common across at least two independent studies. This all provided one of the most comprehensive molecular system views for IPF underlining the regulatory and molecular consequences associated. 56 pathways crosstalks were identified which included critical pathways with specified directionality. The associated steps gained and lost due to crosstalk during IPF were also identified. A serially connected system of five crucial genes was found, potentially controlled by nine miRNAs and eight transcription factors exclusively in IPF when compared to NSIP and Sarcoidosis. Findings from this study have been implemented into a comprehensive molecular and systems database on IPF to facilitate devising diagnostic and therapeutic solutions for this deadly disease.
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