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Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.

Neuron · 2019 · 102(2): 294-320

RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA …

PMID 30998900 DOI ↗

Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA.

Nature communications · 2019 · 10(1): 1338

Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants (GVs) mediating post-transcriptional regulation. Recently, genome-wide detection of in vivo binding of RNA-binding proteins is greatly facilitated by the enhanced crosslinking and immunoprecipitation (eCLIP) method. We developed …

PMID 30902979 DOI ↗

RBP-Maps enables robust generation of splicing regulatory maps.

RNA (New York, N.Y.) · 2019 · 25(2): 193-204

Alternative splicing of pre-messenger RNA transcripts enables the generation of multiple protein isoforms from the same gene locus, providing a major source of protein diversity in mammalian genomes. RNA binding proteins (RBPs) bind to RNA to control splice site choice …

PMID 30413564 DOI ↗

A Transcriptome-wide Translational Program Defined by LIN28B Expression Level.

Molecular cell · 2019 · 73(2): 304-313.e3

LIN28 RNA binding proteins are dynamically expressed throughout mammalian development and during disease. However, it remains unclear how changes in LIN28 expression define patterns of post-transcriptional gene regulation. Here we show that LIN28 expression level is a key variable that …

PMID 30527666 DOI ↗

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Acta neuropathologica · 2018 · 136(3): 405-423

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched …

PMID 29881994 DOI ↗

Sequence, Structure, and Context Preferences of Human RNA Binding Proteins.

Molecular cell · 2018 · 70(5): 854-867.e9

RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present the affinity landscapes of 78 human RBPs using an unbiased assay that determines the sequence, structure, and context preferences of these proteins in vitro by …

PMID 29883606 DOI ↗

Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels.

Molecular cell · 2018 · 69(6): 1005-1016.e7

RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced …

PMID 29547715 DOI ↗

Advances and challenges in the detection of transcriptome-wide protein-RNA interactions.

Wiley interdisciplinary reviews. RNA · 2018 · 9(1)

RNA binding proteins (RBPs) play key roles in determining cellular behavior by manipulating the processing of target RNAs. Robust methods are required to detect the numerous binding sites of RBPs across the transcriptome. RNA-immunoprecipitation followed by sequencing (RIP-seq) and crosslinking …

PMID 28853213 DOI ↗

Erratum to: Robust, Cost-Effective Profiling of RNA Binding Protein Targets with Single-end Enhanced Crosslinking and Immunoprecipitation (seCLIP).

Methods in molecular biology (Clifton, N.J.) · 2017 · 1648: E1

PMID 29230720 DOI ↗

Robust, Cost-Effective Profiling of RNA Binding Protein Targets with Single-end Enhanced Crosslinking and Immunoprecipitation (seCLIP).

Methods in molecular biology (Clifton, N.J.) · 2017 · 1648: 177-200

Profiling of RNA binding protein targets in vivo provides critical insights into the mechanistic roles they play in regulating RNA processing. The enhanced crosslinking and immunoprecipitation (eCLIP) methodology provides a framework for robust, reproducible identification of transcriptome-wide protein-RNA interactions, with …

PMID 28766298 DOI ↗

Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA metabolism.

Nucleic acids research · 2017 · 45(21): 12509-12528

To counteract the breakdown of genome integrity, eukaryotic cells have developed a network of surveillance pathways to prevent and resolve DNA damage. Recent data has recognized the importance of RNA binding proteins (RBPs) in DNA damage repair (DDR) pathways. Here, …

PMID 29069457 DOI ↗

NEAT1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing.

Nature structural & molecular biology · 2017 · 24(10): 816-824

MicroRNA (miRNA) biogenesis is known to be modulated by a variety of RNA-binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. Here, we report that the RNA-binding NONO-PSF …

PMID 28846091 DOI ↗

Genetic mutations in RNA-binding proteins and their roles in ALS.

Human genetics · 2017 · 136(9): 1193-1214

Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of …

PMID 28762175 DOI ↗

The <i>C. elegans</i> neural editome reveals an ADAR target mRNA required for proper chemotaxis.

eLife · 2017 · 6

ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. <i>Caenorhabditis elegans</i> lacking ADARs exhibit …

PMID 28925356 DOI ↗

Variation in single-nucleotide sensitivity of eCLIP derived from reverse transcription conditions.

Methods (San Diego, Calif.) · 2017 · 126: 29-37

Crosslinking and immunoprecipitation (CLIP) followed by high-throughput sequencing identifies the binding sites of RNA binding proteins on RNAs. The covalent RNA-amino acid adducts produced by UV irradiation can cause premature reverse transcription termination and deletions (referred to as crosslink-induced mutation …

PMID 28790018 DOI ↗

CRISPR/Cas9-mediated integration enables TAG-eCLIP of endogenously tagged RNA binding proteins.

Methods (San Diego, Calif.) · 2017 · 118-119: 50-59

Identification of in vivo direct RNA targets for RNA binding proteins (RBPs) provides critical insight into their regulatory activities and mechanisms. Recently, we described a methodology for enhanced crosslinking and immunoprecipitation followed by high-throughput sequencing (eCLIP) using antibodies against endogenous …

PMID 28003131 DOI ↗

Tethered Function Assays as Tools to Elucidate the Molecular Roles of RNA-Binding Proteins.

Advances in experimental medicine and biology · 2016 · 907: 61-88

Dynamic regulation of RNA molecules is critical to the survival and development of cells. Messenger RNAs are transcribed in the nucleus as intron-containing pre-mRNAs and bound by RNA-binding proteins, which control their fate by regulating RNA stability, splicing, polyadenylation, translation, …

PMID 27256382 DOI ↗

Experimental and Computational Considerations in the Study of RNA-Binding Protein-RNA Interactions.

Advances in experimental medicine and biology · 2016 · 907: 1-28

After an RNA is transcribed, it undergoes a variety of processing steps that can change the encoded protein sequence (through alternative splicing and RNA editing), regulate the stability of the RNA, and control subcellular localization, timing, and rate of translation. …

PMID 27256380 DOI ↗

RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

Nature structural & molecular biology · 2016 · 23(12): 1101-1110

Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions …

PMID 27775709 DOI ↗

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

Neuron · 2016 · 92(4): 780-795

HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …

PMID 27773581 DOI ↗

From Protein-RNA Predictions toward a Peptide-RNA Code.

Molecular cell · 2016 · 64(3): 437-438

The RNA field is undergoing a renaissance, with a deluge of proteins being identified to bind RNA. Two reports now introduce proteome-wide approaches that identify the peptides that are crosslinked to RNA (Castello et al., 2016; He et al., 2016).

PMID 27814488 DOI ↗

SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

Molecular cell · 2016 · 64(2): 282-293

RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down …

PMID 27720645 DOI ↗

Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts.

Scientific reports · 2016 · 6: 30896

Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart …

PMID 27485310 DOI ↗

Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.

Nature communications · 2016 · 7: 12143

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs …

PMID 27378374 DOI ↗

Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).

Nature methods · 2016 · 13(6): 508-14

As RNA-binding proteins (RBPs) play essential roles in cellular physiology by interacting with target RNA molecules, binding site identification by UV crosslinking and immunoprecipitation (CLIP) of ribonucleoprotein complexes is critical to understanding RBP function. However, current CLIP protocols are technically …

PMID 27018577 DOI ↗