scholarly journals SMDB: pivotal somatic sequence alterations reprogramming regulatory cascades

NAR Cancer ◽  
2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Limin Jiang ◽  
Mingrui Duan ◽  
Fei Guo ◽  
Jijun Tang ◽  
Olufunmilola Oybamiji ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Translation Regulation ◽  
Single Nucleotide ◽  
Binding Motifs ◽  
Sequence Alteration ◽  
Regulatory Cascades ◽  
Gains And Losses

Abstract Binding motifs for transcription factors, RNA-binding proteins, microRNAs (miRNAs), etc. are vital for proper gene transcription and translation regulation. Sequence alteration mechanisms including single nucleotide mutations, insertion, deletion, RNA editing and single nucleotide polymorphism can lead to gains and losses of binding motifs; such consequentially emerged or vanished binding motifs are termed ‘somatic motifs’ by us. Somatic motifs have been studied sporadically but have never been curated into a comprehensive resource. By analyzing various types of sequence altering data from large consortiums, we successfully identified millions of somatic motifs, including those for important transcription factors, RNA-binding proteins, miRNA seeds and miRNA–mRNA 3′-UTR target motifs. While a few of these somatic motifs have been well studied, our results contain many novel somatic motifs that occur at high frequency and are thus likely to cause important biological repercussions. Genes targeted by these altered motifs are excellent candidates for further mechanism studies. Here, we present the first database that hosts millions of somatic motifs ascribed to a variety of sequence alteration mechanisms.

scholarly journals SBSA: an online service for somatic binding sequence annotation

2021 ◽  
Author(s):  
Limin Jiang ◽  
Fei Guo ◽  
Jijun Tang ◽  
Hui Yu ◽  
Scott Ness ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Human Subjects ◽  
Specific Factor ◽  
Single Nucleotide ◽  
Binding Motifs ◽  
Genomic Variants ◽  
Full Capacity ◽  
Binding Sequence

Abstract Efficient annotation of alterations in binding sequences of molecular regulators can help identify novel candidates for mechanisms study and offer original therapeutic hypotheses. In this work, we developed Somatic Binding Sequence Annotator (SBSA) as a full-capacity online tool to annotate altered binding motifs/sequences, addressing diverse types of genomic variants and molecular regulators. The genomic variants can be somatic mutation, single nucleotide polymorphism, RNA editing, etc. The binding motifs/sequences involve transcription factors (TFs), RNA-binding proteins, miRNA seeds, miRNA-mRNA 3′-UTR binding target, or can be any custom motifs/sequences. Compared to similar tools, SBSA is the first to support miRNA seeds and miRNA-mRNA 3′-UTR binding target, and it unprecedentedly implements a personalized genome approach that accommodates joint adjacent variants. SBSA is empowered to support an indefinite species, including preloaded reference genomes for SARS-Cov-2 and 25 other common organisms. We demonstrated SBSA by annotating multi-omics data from over 30,890 human subjects. Of the millions of somatic binding sequences identified, many are with known severe biological repercussions, such as the somatic mutation in TERT promoter region which causes a gained binding sequence for E26 transformation-specific factor (ETS1). We further validated the function of this TERT mutation using experimental data in cancer cells. Availability:http://innovebioinfo.com/Annotation/SBSA/SBSA.php.

scholarly journals Author response: Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors

2019 ◽  
Author(s):  
Morgan Thompson ◽  
Ryan Bixby ◽  
Robert Dalton ◽  
Alexa Vandenburg ◽  
John A Calarco ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Neuron ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Author Response

scholarly journals Before It Gets Started: Regulating Translation at the 5′ UTR

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Patricia R. Araujo ◽  
Kihoon Yoon ◽  
Daijin Ko ◽  
Andrew D. Smith ◽  
Mei Qiao ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Elements ◽  
Open Reading Frame ◽  
Upstream Open Reading Frame ◽  
Translation Regulation ◽  
Binding Motifs ◽  
Reading Frame ◽  
Physiological Conditions ◽  
The Impact

Translation regulation plays important roles in both normal physiological conditions and diseases states. This regulation requires cis-regulatory elements located mostly in 5′ and 3′ UTRs and trans-regulatory factors (e.g., RNA binding proteins (RBPs)) which recognize specific RNA features and interact with the translation machinery to modulate its activity. In this paper, we discuss important aspects of 5′ UTR-mediated regulation by providing an overview of the characteristics and the function of the main elements present in this region, like uORF (upstream open reading frame), secondary structures, and RBPs binding motifs and different mechanisms of translation regulation and the impact they have on gene expression and human health when deregulated.

scholarly journals Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Morgan Thompson ◽  
Ryan Bixby ◽  
Robert Dalton ◽  
Alexa Vandenburg ◽  
John A Calarco ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Single Neuron ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Fluorescent Reporters ◽  
Post Transcriptional Regulation ◽  
Splicing Patterns ◽  
Phenotypic Convergence

Single-cell transcriptomes are established by transcription factors (TFs), which determine a cell's gene-expression complement. Post-transcriptional regulation of single-cell transcriptomes, and the RNA binding proteins (RBPs) responsible, are more technically challenging to determine, and combinatorial TF-RBP coordination of single-cell transcriptomes remains unexplored. We used fluorescent reporters to visualize alternative splicing in single Caenorhabditis elegans neurons, identifying complex splicing patterns in the neuronal kinase sad-1. Most neurons express both isoforms, but the ALM mechanosensory neuron expresses only the exon-included isoform, while its developmental sister cell the BDU neuron expresses only the exon-skipped isoform. A cascade of three cell-specific TFs and two RBPs are combinatorially required for sad-1 exon inclusion. Mechanistically, TFs combinatorially ensure expression of RBPs, which interact with sad-1 pre-mRNA. Thus a combinatorial TF-RBP code controls single-neuron sad-1 splicing. Additionally, we find ‘phenotypic convergence,’ previously observed for TFs, also applies to RBPs: different RBP combinations generate similar splicing outcomes in different neurons.

scholarly journals RNA-mediated gene regulation is less evolvable than transcriptional regulation

2018 ◽  
Vol 115 (15) ◽  
pp. E3481-E3490 ◽  
Author(s):  
Joshua L. Payne ◽  
Fahad Khalid ◽  
Andreas Wagner
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Protein ◽  
Regulatory Region

Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein–RNA interactions and transcription factor–DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.

Sign in / Sign up

Export Citation Format

Share Document