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How RNA-Binding Proteins Interact with RNA: Molecules and Mechanisms.

Molecular cell · 2020 · 78(1): 9-29

RNA-binding proteins (RBPs) comprise a large class of over 2,000 proteins that interact with transcripts in all manner of RNA-driven processes. The structures and mechanisms that RBPs use to bind and regulate RNA are incredibly diverse. In this review, we …

PMID 32243832 DOI ↗

The mRNA Decay Factor CAR-1/LSM14 Regulates Axon Regeneration via Mitochondrial Calcium Dynamics.

Current biology : CB · 2020 · 30(5): 865-876.e7

mRNA decay factors regulate mRNA turnover by recruiting non-translating mRNAs and targeting them for translational repression and mRNA degradation. How mRNA decay pathways regulate cellular function in vivo with specificity is poorly understood. Here, we show that C. elegans mRNA …

PMID 31983639 DOI ↗

Regulation of RNA editing by RNA-binding proteins in human cells.

Communications biology · 2019 · 2: 19

Adenosine-to-inosine (A-to-I) editing, mediated by the ADAR enzymes, diversifies the transcriptome by altering RNA sequences. Recent studies reported global changes in RNA editing in disease and development. Such widespread editing variations necessitate an improved understanding of the regulatory mechanisms of …

PMID 30652130 DOI ↗

Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells.

Angewandte Chemie (International ed. in English) · 2019 · 58(44): 15646-15649

The scarcity of effective means to deliver functional proteins to living cells is a central problem in biotechnology and medicine. Herein, we report the efficient delivery of an active DNA-modifying enzyme to human stem cells through high-density cell penetrating peptide …

PMID 31404473 DOI ↗

Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD.

Neuron · 2019 · 103(5): 802-819.e11

Stress granules (SGs) form during cellular stress and are implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). To yield insights into the role of SGs in pathophysiology, we performed a high-content screen to identify small …

PMID 31272829 DOI ↗

A protein-RNA interaction atlas of the ribosome biogenesis factor AATF.

Scientific reports · 2019 · 9(1): 11071

AATF is a central regulator of the cellular outcome upon p53 activation, a finding that has primarily been attributed to its function as a transcription factor. Recent data showed that AATF is essential for ribosome biogenesis and plays a role …

PMID 31363146 DOI ↗

Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription.

Cell · 2019 · 178(1): 107-121.e18

Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA-binding proteins (RBPs). Although multiple RBPs have been implicated in transcription control, it has remained unclear how extensively RBPs directly act on …

PMID 31251911 DOI ↗

Active Protein Neddylation or Ubiquitylation Is Dispensable for Stress Granule Dynamics.

Cell reports · 2019 · 27(5): 1356-1363.e3

Stress granule (SG) formation is frequently accompanied by ubiquitin proteasome system (UPS) impairment and ubiquitylated protein accumulation. SGs, ubiquitin, and UPS components co-localize, but the relationship between the ubiquitin pathway and SGs has not been systematically characterized. We utilize pharmacological …

PMID 31042464 DOI ↗

Disruption in A-to-I Editing Levels Affects C. elegans Development More Than a Complete Lack of Editing.

Cell reports · 2019 · 27(4): 1244-1253.e4

A-to-I RNA editing, catalyzed by ADAR proteins, is widespread in eukaryotic transcriptomes. Studies showed that, in C. elegans, ADR-2 can actively deaminate dsRNA, whereas ADR-1 cannot. Therefore, we set out to study the effect of each of the ADAR genes …

PMID 31018137 DOI ↗

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 ↗

Overriding FUS autoregulation in mice triggers gain-of-toxic dysfunctions in RNA metabolism and autophagy-lysosome axis.

eLife · 2019 · 8

Mutations in coding and non-coding regions of FUS cause amyotrophic lateral sclerosis (ALS). The latter mutations may exert toxicity by increasing FUS accumulation. We show here that broad expression within the nervous system of wild-type or either of two ALS-linked …

PMID 30747709 DOI ↗

Widespread RNA editing dysregulation in brains from autistic individuals.

Nature neuroscience · 2019 · 22(1): 25-36

Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns …

PMID 30559470 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 ↗

Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.

Cell · 2018 · 172(3): 590-604.e13

Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, …

PMID 29373831 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 ↗

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 ↗

Short poly(A) tails are a conserved feature of highly expressed genes.

Nature structural & molecular biology · 2017 · 24(12): 1057-1063

Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not associated with translational efficiency in nonembryonic cells. To investigate whether poly(A) tail size might be coupled to …

PMID 29106412 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 ↗