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320 results
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Long-read Ribo-STAMP simultaneously measures transcription and translation with isoform resolution.
Genome research · 2024 · 34(11): 2012-2024
Transcription and translation are intertwined processes in which mRNA isoforms are crucial intermediaries. However, methodological limitations in analyzing translation at the mRNA isoform level have left gaps in our understanding of critical biological processes. To address these gaps, we developed …
PMID 38906680 DOI ↗
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Localized synthesis of molecular chaperones sustains neuronal proteostasis.
bioRxiv : the preprint server for biology · 2024
Neurons are challenged to maintain proteostasis in neuronal projections, particularly with the physiological stress at synapses to support intercellular communication underlying important functions such as memory and movement control. Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted …
PMID 37873158 DOI ↗
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Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.
Molecular cell · 2024 · 84(19): 3826-3842.e8
RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and …
PMID 39303722 DOI ↗
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Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.
Molecular cell · 2024 · 84(19): 3790-3809.e8
mRNAs interact with RNA-binding proteins (RBPs) throughout their processing and maturation. While efforts have assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware, RBP-centric PPI map …
PMID 39303721 DOI ↗
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Author Correction: Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.
Nature biotechnology · 2024 · 42(9): 1467
PMID 38418649 DOI ↗
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Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.
Nature biotechnology · 2024 · 42(9): 1429-1441
RNA-binding proteins (RBPs) modulate alternative splicing outcomes to determine isoform expression and cellular survival. To identify RBPs that directly drive alternative exon inclusion, we developed tethered function luciferase-based splicing reporters that provide rapid, scalable and robust readouts of exon inclusion …
PMID 38168984 DOI ↗
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Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.
Cell reports · 2024 · 43(8): 114637
Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder …
PMID 39154337 DOI ↗
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Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling.
Proceedings of the National Academy of Sciences of the United States of America · 2024 · 121(34): e2319724121
Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and …
PMID 39141348 DOI ↗
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High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues.
Nature communications · 2024 · 15(1): 7067
RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through …
PMID 39152130 DOI ↗
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Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.
Cell genomics · 2024 · 4(7): 100603
The uncovering of protein-RNA interactions enables a deeper understanding of RNA processing. Recent multiplexed crosslinking and immunoprecipitation (CLIP) technologies such as antibody-barcoded eCLIP (ABC) dramatically increase the throughput of mapping RNA binding protein (RBP) binding sites. However, multiplex CLIP datasets …
PMID 38955188 DOI ↗
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Epistatic interactions between NMD and TRP53 control progenitor cell maintenance and brain size.
Neuron · 2024 · 112(13): 2157-2176.e12
Mutations in human nonsense-mediated mRNA decay (NMD) factors are enriched in neurodevelopmental disorders. We show that deletion of key NMD factor Upf2 in mouse embryonic neural progenitor cells causes perinatal microcephaly but deletion in immature neurons does not, indicating NMD's …
PMID 38697111 DOI ↗
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Protocol to process crosslinking and immunoprecipitation data into annotated binding sites.
STAR protocols · 2024 · 5(2): 103040
Here, we present a protocol for using Skipper, a pipeline designed to process crosslinking and immunoprecipitation (CLIP) data into annotated binding sites. We describe steps for partitioning annotated transcript regions and fitting data to a beta-binomial model to call windows …
PMID 38669139 DOI ↗
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Small nuclear RNAs enhance protein-free RNA-programmable base conversion on mammalian coding transcripts.
bioRxiv : the preprint server for biology · 2024
Endogenous U small nuclear RNAs (U snRNAs) form RNA-protein complexes responsible for eukaryotic processing of pre-mRNA into mature mRNA. Previous studies have demonstrated the utility of guide-programmable U snRNAs in targeted exon inclusion and exclusion. We investigated whether snRNAs can …
PMID 38915553 DOI ↗
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circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.
bioRxiv : the preprint server for biology · 2024
Circular RNAs (circRNAs) represent a class of widespread endogenous RNAs that regulate gene expression and thereby influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses …
PMID 37745562 DOI ↗
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ePRINT: exonuclease assisted mapping of protein-RNA interactions.
Genome biology · 2024 · 25(1): 140
RNA-binding proteins (RBPs) regulate key aspects of RNA processing including alternative splicing, mRNA degradation and localization by physically binding RNA molecules. Current methods to map these interactions, such as CLIP, rely on purifying single proteins at a time. Our new …
PMID 38807229 DOI ↗
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A phage nucleus-associated RNA-binding protein is required for jumbo phage infection.
Nucleic acids research · 2024 · 52(8): 4440-4455
Large-genome bacteriophages (jumbo phages) of the proposed family Chimalliviridae assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and DNA-targeting CRISPR-Cas nucleases. While the nuclear shell provides broad protection against …
PMID 38554115 DOI ↗
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Transcriptome regulation by PARP13 in basal and antiviral states in human cells.
iScience · 2024 · 27(4): 109251
The RNA-binding protein PARP13 is a primary factor in the innate antiviral response, which suppresses translation and drives decay of bound viral and host RNA. PARP13 interacts with many proteins encoded by interferon-stimulated genes (ISG) to activate antiviral pathways including …
PMID 38495826 DOI ↗
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Bento: a toolkit for subcellular analysis of spatial transcriptomics data.
Genome biology · 2024 · 25(1): 82
The spatial organization of molecules in a cell is essential for their functions. While current methods focus on discerning tissue architecture, cell-cell interactions, and spatial expression patterns, they are limited to the multicellular scale. We present Bento, a Python toolkit …
PMID 38566187 DOI ↗
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Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted.
bioRxiv : the preprint server for biology · 2024
Tissue-resident memory CD8 T cells (T<sub>RM</sub>) kill infected cells and recruit additional immune cells to limit pathogen invasion at barrier sites. Small intestinal (SI) T<sub>RM</sub> cells consist of distinct subpopulations with higher expression of effector molecules or greater memory potential. …
PMID 38585842 DOI ↗
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Computational cell-cell interaction technologies drive mechanistic and biomarker discovery in the tumor microenvironment.
Current opinion in biotechnology · 2024 · 85: 103048
Complex networks of cell-cell interactions (CCIs) within the tumor microenvironment (TME) play a crucial role in cancer persistence. These communication axes represent prime targets for therapeutic intervention, but our incomplete understanding of the cellular heterogeneity and interacting partners within the …
PMID 38142648 DOI ↗
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LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function.
RNA (New York, N.Y.) · 2024 · 30(3): 223-239
Mitochondria-associated RNA-binding proteins (RBPs) have emerged as key contributors to mitochondrial biogenesis and homeostasis. With few examples known, we set out to identify RBPs that regulate nuclear-encoded mitochondrial mRNAs (NEMmRNAs). Our systematic analysis of RNA targets of 150 RBPs identified …
PMID 38164626 DOI ↗
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Expanded palette of RNA base editors for comprehensive RBP-RNA interactome studies.
Nature communications · 2024 · 15(1): 875
RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and STAMP (surveying targets by APOBEC1 mediated profiling) utilize …
PMID 38287010 DOI ↗
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Junior scientists spotlight social bonds in seminars for diversity, equity, and inclusion in STEM.
PloS one · 2023 · 18(11): e0293322
Disparities for women and minorities in science, technology, engineering, and math (STEM) careers have continued even amidst mounting evidence for the superior performance of diverse workforces. In response, we launched the Diversity and Science Lecture series, a cross-institutional platform where …
PMID 37917746 DOI ↗
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Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.
Cell · 2023 · 186(26): 5690-5704.e20
The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency …
PMID 38101407 DOI ↗
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Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery.
Nucleic acids research · 2023 · 51(19): 10768-10781
Translational readthrough of UGA stop codons by selenocysteine-specific tRNA (tRNASec) enables the synthesis of selenoproteins. Seryl-tRNA synthetase (SerRS) charges tRNASec with serine, which is modified into selenocysteine and delivered to the ribosome by a designated elongation factor (eEFSec in eukaryotes). …
PMID 37739431 DOI ↗