RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory networks.High-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent pow...RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory networks.High-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA interactions.However,assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins(RBPs)remains technically challenging.Chemical modifications to mRNA also play important roles in regulating gene expression.Investigation of the functional roles of these modifications relies highly on the detection methods used.RNA structure is also critical at nearly every step of the RNA life cycle.In this review,we summarize recent advances and limitations in CLIP technologies and discuss the computational challenges of and bioinformatics tools used for decoding the functions and regulatory networks of ncRNAs.We also summarize methods used to detect RNA modifications and to probe RNA structure.展开更多
Background:RNA binding proteins(RBPs)play essential roles in the regulation of RNA metabolism.Recent studies have disclosed that RBPs achieve their functions via binding to their targets in a position-dependent patter...Background:RNA binding proteins(RBPs)play essential roles in the regulation of RNA metabolism.Recent studies have disclosed that RBPs achieve their functions via binding to their targets in a position-dependent pattern on RNAs.However,few studies have systematially addressed the associations between the RBP's functions and their positional binding preferences.Methods:Here,we present large-scale analyses on the functional targets of human RBPs by integrating the enhanced cross-linking and immunoprecipitation followed by sequencing(eCLIP-seq)datasets and the shRNA knockdown followed by RNA-seq datasets that are deposited in the integrated ENCyclopedia of DNA Elements in the human genome(ENCODE)data portal.Results:We found that(1)binding to the translation termination site and the 3'untranslated region is important to most human RBP's in the RNA decay regulation;(2)RBPs’binding and regulation follow a cell-ty pe specific pattern.Conclusions:These analysis results show the strong relationship between the binding position and the functions of RBPs,which provides novel insights into the RBPs'regulation mechanisms.展开更多
文摘RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory networks.High-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA interactions.However,assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins(RBPs)remains technically challenging.Chemical modifications to mRNA also play important roles in regulating gene expression.Investigation of the functional roles of these modifications relies highly on the detection methods used.RNA structure is also critical at nearly every step of the RNA life cycle.In this review,we summarize recent advances and limitations in CLIP technologies and discuss the computational challenges of and bioinformatics tools used for decoding the functions and regulatory networks of ncRNAs.We also summarize methods used to detect RNA modifications and to probe RNA structure.
基金Z.O.acknowledges the National Institute of General Medical Sciences(https://www.nigms.nih.gov/)grant R35GM124998.
文摘Background:RNA binding proteins(RBPs)play essential roles in the regulation of RNA metabolism.Recent studies have disclosed that RBPs achieve their functions via binding to their targets in a position-dependent pattern on RNAs.However,few studies have systematially addressed the associations between the RBP's functions and their positional binding preferences.Methods:Here,we present large-scale analyses on the functional targets of human RBPs by integrating the enhanced cross-linking and immunoprecipitation followed by sequencing(eCLIP-seq)datasets and the shRNA knockdown followed by RNA-seq datasets that are deposited in the integrated ENCyclopedia of DNA Elements in the human genome(ENCODE)data portal.Results:We found that(1)binding to the translation termination site and the 3'untranslated region is important to most human RBP's in the RNA decay regulation;(2)RBPs’binding and regulation follow a cell-ty pe specific pattern.Conclusions:These analysis results show the strong relationship between the binding position and the functions of RBPs,which provides novel insights into the RBPs'regulation mechanisms.