Mechanistic Dissection of RNA-Binding Proteins in Regulated Gene Expression at Chromatin Levels
Year: 2019
Type: preprint
Abstract: Eukaryotic genomes are known to prevalently transcribe diverse classes of RNAs, virtually all of which, including nascent RNAs from protein-coding genes, are now recognized to have regulatory functions in gene expression, suggesting that RNAs are both the products and the regulators of gene expression.Their functions must enlist specific RNA-binding proteins (RBPs) to execute their regulatory activities, and recent evidence suggests that nearly all biochemically defined chromatin regions in the human genome, whether defined for gene activation or silencing, have the involvement of specific RBPs.Interestingly, the boundary between RNA-and DNA-binding proteins is also melting, as many DNA-binding proteins traditionally studied in the context of transcription are able to bind RNAs, some of which may simultaneously bind both DNA and RNA to facilitate network interactions in three-dimensional (3D) genome.In this review, we focus on RBPs that function at chromatin levels, with particular emphasis on their mechanisms of action in regulated gene expression, which is intended to facilitate future functional and mechanistic dissection of chromatin-associated RBPs.The traditional view of transcription is to produce either structural RNAs or protein-coding mRNAs.Specific structural RNAs are assembled into various RNA machines to catalyze specific biochemical reactions, and protein-coding RNAs are processed in the nucleus (such as capping, splicing, and polyadenylation) and then exported to the cytoplasm to translate into proteins.The advent of deepsequencing technologies has now revealed that mammalian genomes are far more active in transcription ( Djebaliet al. 2012), generating a large repertoire of regulatory RNAs, including long noncoding RNAs (lncRNAs) (Long et al. 2017), repeat-derived RNAs (Johnson and Straight 2017), and enhancer RNAs (eRNAs) (Li et al. 2016).Even protein-coding genes are producing various smaller RNA species that are either cause or consequence of regulated gene expression as a result of divergent or convergent transcription and transcription pausing and pause release (Wissink et al. 2019).Most regulatory RNAs are predominantly retained in the nucleus (Li and Fu 2019), where they may modulate gene expression at different steps of transcription on specific transcription units or genomic loci (Skalska et al. 2017), remodel chromatin structures and dynamics (Bohmdorfer and Wierzbicki 2015), and mediate long-distance genomic
Authors: Jia-Yu Chen, Do-Hwan Lim, Xiang-Dong Fu
Institution: University of California San Diego
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2996921649