scholarly journals Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Eric L. Van Nostrand ◽  
Gabriel A. Pratt ◽  
Brian A. Yee ◽  
Emily C. Wheeler ◽  
Steven M. Blue ◽  
...  
Keyword(s):  
Rna Processing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins

RNA-Binding Proteins Required for Chloroplast RNA Processing

2010 ◽  
pp. 177-203 ◽  
Author(s):  
Reimo Zoschke ◽  
Christiane Kupsch ◽  
Christian Schmitz-Linneweber
Keyword(s):  
Rna Processing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Chloroplast Rna

scholarly journals RNA-Binding Proteins in Amyotrophic Lateral Sclerosis and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Scott E. Ugras ◽  
James Shorter
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disease ◽  
Rna Processing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Future Studies ◽  
Inclusion Formation ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is an adult onset neurodegenerative disease, which is universally fatal. While the causes of this devastating disease are poorly understood, recent advances have implicated RNA-binding proteins (RBPs) that contain predicted prion domains as a major culprit. Specifically, mutations in the RBPs TDP-43 and FUS can cause ALS. Cytoplasmic mislocalization and inclusion formation are common pathological features of TDP-43 and FUS proteinopathies. Though these RBPs share striking pathological and structural similarities, considerable evidence suggests that the ALS-linked mutations in TDP-43 and FUS can cause disease by disparate mechanisms. In a recent study, Couthouis et al. screened for protein candidates that were also involved in RNA processing, contained a predicted prion domain, shared other phenotypic similarities with TDP-43 and FUS, and identified TAF15 as a putative ALS gene. Subsequent sequencing of ALS patients successfully identified ALS-linked mutations in TAF15 that were largely absent in control populations. This study underscores the important role that perturbations in RNA metabolism might play in neurodegeneration, and it raises the possibility that future studies will identify other RBPs with critical roles in neurodegenerative disease.

Coupling genetics and post-genomic approaches to decipher the cellular splicing code at a systems-wide level

2010 ◽  
Vol 38 (1) ◽  
pp. 237-241 ◽  
Author(s):  
Yilei Liu ◽  
David J. Elliott
Keyword(s):  
Rna Processing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Eukaryotic Gene Expression ◽  
Nuclear Rna ◽  
Processing Pathways ◽  
Eukaryotic Gene ◽  
Alternatively Spliced ◽  
Nuclear Rna Processing

Nuclear RNA processing is a critical stage in eukaryotic gene expression, and is controlled in part by the expression and concentration of nuclear RNA-binding proteins. Different nuclear RNA-binding proteins are differentially expressed in different cells, helping the spliceosome to decode pre-mRNAs into alternatively spliced mRNAs. Recent post-genomic technology has exposed the complexity of nuclear RNA processing, and is starting to reveal the mechanisms and rules through which networks of RNA-binding proteins can regulate multiple parallel pathways. Identification of multiple parallel processing pathways regulated by nuclear RNA-binding proteins is leading to a systems-wide understanding of the rules and consequences of alternative nuclear RNA processing.

scholarly journals Calreticulin Interacts with C/EBPα and C/EBPβ mRNAs and Represses Translation of C/EBP Proteins

2002 ◽  
Vol 22 (20) ◽  
pp. 7242-7257 ◽  
Author(s):  
Lubov T. Timchenko ◽  
Polina Iakova ◽  
Alana L. Welm ◽  
Z.-J. Cai ◽  
Nikolai A. Timchenko
Keyword(s):  
Rna Processing ◽  
Posttranscriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Posttranscriptional Control ◽  
Multifunctional Protein ◽  
Virus Rna

ABSTRACT We previously identified an RNA binding protein, CUGBP1, which binds to GCN repeats located within the 5′ region of C/EBPβ mRNAs and regulates translation of C/EBPβ isoforms. To further investigate the role of RNA binding proteins in the posttranscriptional control of C/EBP proteins, we purified additional RNA binding proteins that interact with GC-rich RNAs and that may regulate RNA processing. In HeLa cells, the majority of GC-rich RNA binding proteins are associated with endogenous RNA transcripts. The separation of these proteins from endogenous RNA identified several proteins in addition to CUGBP1 that specifically interact with the GC-rich 5′ region of C/EBPβ mRNA. One of these proteins was purified to homogeneity and was identified as calreticulin (CRT). CRT is a multifunctional protein involved in several biological processes, including interaction with and regulation of rubella virus RNA processing. Our data demonstrate that both CUGBP1 and CRT interact with GCU repeats within myotonin protein kinase and with GCN repeats within C/EBPα and C/EBPβ mRNAs. GCN repeats within these mRNAs form stable SL structures. The interaction of CRT with SL structures of C/EBPβ and C/EBPα mRNAs leads to inhibition of translation of C/EBP proteins in vitro and in vivo. Deletions or mutations abolishing the formation of SL structures within C/EBPα and C/EBPβ mRNAs lead to a failure of CRT to inhibit translation of C/EBP proteins. CRT-dependent inhibition of C/EBPα is sufficient to block the growth-inhibitory activity of C/EBPα. This finding further defines the molecular mechanism for posttranscriptional regulation of the C/EBPα and C/EBPβ proteins.

scholarly journals Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

2019 ◽  
Author(s):  
Eric L Van Nostrand ◽  
Gabriel A Pratt ◽  
Brian A Yee ◽  
Emily Wheeler ◽  
Steven M Blue ◽  
...  
Keyword(s):  
Rna Processing ◽  
Regulatory Networks ◽  
Large Scale ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cell Types ◽  
Integrated Analysis ◽  
Branch Points

AbstractA critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enabled mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale integrated analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the large-scale mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. Here we describe our analysis of 223 enhanced (eCLIP) datasets characterizing 150 RBPs in K562 and HepG2 cell lines, revealing a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multi-copy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation (enabling identification of branch points with single-nucleotide resolution) and provides genome-wide validation for a branch point-based scanning model for 3’ splice site recognition. Further, we show that eCLIP peak co-occurrences across RBPs enables the discovery of novel co-interacting RBPs. Finally, we present a protocol for visualization of RBP:RNA complexes in the eCLIP workflow using biotin and standard chemiluminescent visualization reagents, enabling simplified confirmation of ribonucleoprotein enrichment without radioactivity. This work illustrates the value of integrated analysis across eCLIP profiling of RBPs with widely distinct functions to reveal novel RNA biology. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.

scholarly journals Drosophila as a Model for Assessing the Function of RNA-Binding Proteins during Neurogenesis and Neurological Disease

2018 ◽  
Vol 6 (3) ◽  
pp. 21 ◽  
Author(s):  
Eugenia Olesnicky ◽  
Ethan Wright
Keyword(s):  
Rna Processing ◽  
Rna Splicing ◽  
Neurological Disease ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Asymmetric Cell Division ◽  
Rna Binding Proteins ◽  
Muscular Atrophy ◽  
Messenger Rnas

An outstanding question in developmental neurobiology is how RNA processing events contribute to the regulation of neurogenesis. RNA processing events are increasingly recognized as playing fundamental roles in regulating multiple developmental events during neurogenesis, from the asymmetric divisions of neural stem cells, to the generation of complex and diverse neurite morphologies. Indeed, both asymmetric cell division and neurite morphogenesis are often achieved by mechanisms that generate asymmetric protein distributions, including post-transcriptional gene regulatory mechanisms such as the transport of translationally silent messenger RNAs (mRNAs) and local translation of mRNAs within neurites. Additionally, defects in RNA splicing have emerged as a common theme in many neurodegenerative disorders, highlighting the importance of RNA processing in maintaining neuronal circuitry. RNA-binding proteins (RBPs) play an integral role in splicing and post-transcriptional gene regulation, and mutations in RBPs have been linked with multiple neurological disorders including autism, dementia, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Fragile X syndrome (FXS), and X-linked intellectual disability disorder. Despite their widespread nature and roles in neurological disease, the molecular mechanisms and networks of regulated target RNAs have been defined for only a small number of specific RBPs. This review aims to highlight recent studies in Drosophila that have advanced our knowledge of how RBP dysfunction contributes to neurological disease.

scholarly journals Molecular Network Analysis Suggests a Logical Hypothesis for the Pathological Role of C9orf72 in Amyotrophic Lateral Sclerosis/Frontotemporal Dementia

2014 ◽  
Vol 6 ◽  
pp. JCNSD.S18103 ◽  
Author(s):  
Jun-Ichi Satoh ◽  
Yoji Yamamoto ◽  
Shouta Kitano ◽  
Mika Takitani ◽  
Naohiro Asahina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Amyotrophic Lateral Sclerosis ◽  
Frontotemporal Dementia ◽  
Motor Neurons ◽  
Rna Processing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cytoskeletal Dynamics ◽  
Lateral Sclerosis

Background Expanded GGGGCC hexanucleotide repeats, ranging from hundreds to thousands in number, located in the noncoding region of the chromosome 9 open reading frame 72 ( C9orf72) gene represent the most common genetic abnormality for familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (abbreviated as C9ALS). Currently, three pathological mechanisms, such as haplo insufficiency of C9orf72, formation of nuclear RNA foci composed of sense and antisense repeats, and accumulation of unconventionally transcribed dipeptide-repeat (DPR) proteins, are proposed for C9ALS. However, at present, the central mechanism underlying neurodegeneration in C9ALS remains largely unknown. Methods By using three distinct pathway analysis tools of bioinformatics, we studied molecular networks involved in C9ALS pathology by focusing on C9orf72 omics datasets, such as proteome of C9orf72 repeat RNA-binding proteins, transcriptome of induced pluripotent stem cells (iPSC)-derived motor neurons of patients with C9ALS, and transcriptome of purified motor neurons of patients with C9ALS. Results We found that C9orf72 repeat RNA-binding proteins play a crucial role in the regulation of post-transcriptional RNA processing. The expression of a wide range of extracellular matrix proteins and matrix metalloproteinases was reduced in iPSC-derived motor neurons of patients with C9ALS. The regulation of RNA processing and cytoskeletal dynamics is disturbed in motor neurons of patients with C9ALS in vivo. Conclusions Bioinformatics data mining approach suggests a logical hypothesis that C9orf72 repeat expansions that deregulate post-transcriptional RNA processing disturb the homeostasis of cytoskeletal dynamics and remodeling of extracellular matrix, leading to degeneration of stress-vulnerable neurons in the brain and spinal cord of patients with C9ALS.

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