Institution
Howard Hughes Medical Institute
Nonprofit•Chevy Chase, Maryland, United States•
About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.
Topics: Gene, RNA, Population, Cellular differentiation, Transcription factor
Papers published on a yearly basis
Papers
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TL;DR: It is found that m6A alters the local structure in mRNA and long non-coding RNA (lncRNA) to facilitate binding of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an abundant nuclear RNA-binding protein responsible for pre-mRNA processing.
Abstract: RNA-binding proteins control many aspects of cellular biology through binding single-stranded RNA binding motifs (RBMs). However, RBMs can be buried within their local RNA structures, thus inhibiting RNA-protein interactions. N(6)-methyladenosine (m(6)A), the most abundant and dynamic internal modification in eukaryotic messenger RNA, can be selectively recognized by the YTHDF2 protein to affect the stability of cytoplasmic mRNAs, but how m(6)A achieves its wide-ranging physiological role needs further exploration. Here we show in human cells that m(6)A controls the RNA-structure-dependent accessibility of RBMs to affect RNA-protein interactions for biological regulation; we term this mechanism 'the m(6)A-switch'. We found that m(6)A alters the local structure in mRNA and long non-coding RNA (lncRNA) to facilitate binding of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an abundant nuclear RNA-binding protein responsible for pre-mRNA processing. Combining photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) and anti-m(6)A immunoprecipitation (MeRIP) approaches enabled us to identify 39,060 m(6)A-switches among HNRNPC-binding sites; and global m(6)A reduction decreased HNRNPC binding at 2,798 high-confidence m(6)A-switches. We determined that these m(6)A-switch-regulated HNRNPC-binding activities affect the abundance as well as alternative splicing of target mRNAs, demonstrating the regulatory role of m(6)A-switches on gene expression and RNA maturation. Our results illustrate how RNA-binding proteins gain regulated access to their RBMs through m(6)A-dependent RNA structural remodelling, and provide a new direction for investigating RNA-modification-coded cellular biology.
1,313 citations
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TL;DR: A genome-wide means of mapping protein–RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP), which revealed a large number of Nova–RNA interactions in 3′ untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain.
Abstract: Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.
1,313 citations
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TL;DR: An emerging model of cytoplasmic mRNA function is suggested in which the rates of translation and degradation of mRNAs are influenced by a dynamic equilibrium between polysomes and the mRNPs seen in P bodies.
1,311 citations
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TL;DR: It is found that a switch from an M1- to an M2-dominant response occurred in microglia and peripherally derived macrophages as remyelination started and activin-A is identified as a therapeutic target for CNS regeneration.
Abstract: In this study, the authors show that oligodendrocyte differentiation and remyelination after a CNS lesion coincides with a switch in microglial/macrophage polarization from a pro-inflammatory, M1, phenotype to an anti-inflammatory, M2, phenotype. This M2-dependant effect was in part mediated by secretion of the TGFβ family member, Activin-A.
1,310 citations
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TL;DR: The aim of this monograph is to clarify the role of Incretin in the development of Glucagon-Related Peptides in women and to provide a mechanistic basis for future research into their role in women's health.
Abstract: I. Introduction II. History of the Incretin Concept: Discovery of Gastric Inhibitory Polypeptide III. Discovery of GLP-1 IV. Structures of GLPs and Family of Glucagon-Related Peptides V. Tissue Distribution of the Expression of GLPs A. Pancreatic α-cells B. Intestinal L cells C. Central nervous system VI. Proglucagon Biosynthesis A. Organization/structure of the proglucagon gene B. Regulation of glucagon gene expression C. Posttranslational processing of proglucagon VII. Regulation of GLP Secretion A. Overview B. Intracellular signals C. Carbohydrates D. Fats E. Proteins F. Endocrine G. Neural H. GLP-2 VIII. Metabolism of GLPs A. GLP-1 B. GLP-2 IX. Physiological Actions of GLPs A. Overview B. Pancreatic islets C. Counterregulatory actions of GLP-1 and leptin on β-cells D. Stomach E. Lung F. Brain G. Liver, skeletal muscle, and fat H. Pituitary, hypothalamus, and thyroid I. Cardiovascular system J. GLP-2 X. GLP Receptors A. Structure B. Signaling C. Distribution D. Regulation E. GLP-2 XI. Pathophysiology o...
1,308 citations
Authors
Showing all 20486 results
Name | H-index | Papers | Citations |
---|---|---|---|
Bert Vogelstein | 247 | 757 | 332094 |
Richard A. Flavell | 231 | 1328 | 205119 |
Steven A. Rosenberg | 218 | 1204 | 199262 |
Kenneth W. Kinzler | 215 | 640 | 243944 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Rob Knight | 201 | 1061 | 253207 |
Irving L. Weissman | 201 | 1141 | 172504 |
Ronald M. Evans | 199 | 708 | 166722 |
Francis S. Collins | 196 | 743 | 250787 |
Craig B. Thompson | 195 | 557 | 173172 |
Thomas C. Südhof | 191 | 653 | 118007 |
Joan Massagué | 189 | 408 | 149951 |
Stuart H. Orkin | 186 | 715 | 112182 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Eric R. Kandel | 184 | 603 | 113560 |