Journal ArticleDOI
ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation
Hasem Habelhah,Kavita Shah,Lan Huang,Antje Ostareck-Lederer,Alma L. Burlingame,Kevan M. Shokat,Matthias W. Hentze,Ze'ev Ronai +7 more
TLDR
The role of MAPK/ERK is established in phosphorylation-dependent cellular localization of hnRNP-K, which is required for its ability to silence mRNA translation.Abstract:
Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) is one of a family of 20 proteins that are involved in transcription and post-transcriptional messenger RNA metabolism. The mechanisms that underlie regulation of hnRNP-K activities remain largely unknown. Here we show that cytoplasmic accumulation of hnRNP-K is phosphorylation-dependent. Mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) efficiently phosphorylates hnRNP-K both in vitro and in vivo at serines 284 and 353. Serum stimulation or constitutive activation of ERK kinase (MEK1) results in phosphorylation and cytoplasmic accumulation of hnRNP-K. Mutation at ERK phosphoacceptor sites in hnRNP-K abolishes the ability to accumulate in the cytoplasm and renders the protein incapable of regulating translation of mRNAs that have a differentiation-control element (DICE) in the 3' untranslated region (UTR). Similarly, treatment with a pharmacological inhibitor of the ERK pathway abolishes cytoplasmic accumulation of hnRNP-K and attenuates inhibition of mRNA translation. Our results establish the role of MAPK/ERK in phosphorylation-dependent cellular localization of hnRNP-K, which is required for its ability to silence mRNA translation.read more
Citations
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Journal ArticleDOI
Messenger-RNA-binding proteins and the messages they carry.
TL;DR: From sites of transcription in the nucleus to the outreaches of the cytoplasm, messenger RNAs are associated with RNA-binding proteins that communicate crucial information to the translation machinery for the surveillance of nonsense mutations and for mRNA localization and translation.
Book
Neural Control Of Renal Function
Gerald F. DiBona,Ulla C. Kopp +1 more
TL;DR: The renal nerve is the communication link between the central nervous system and the kidney as discussed by the authors, which is the major structural and functional components of the kidney, the vessels, glomeruli, and tubules, each of which is innervated.
Journal ArticleDOI
The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions
Seunghee Yoon,Rony Seger +1 more
TL;DR: Understanding of these processes may provide a full picture of the distinct, and even opposing cellular processes that are regulated by the ERK cascade, which is described in the current review.
Journal ArticleDOI
Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
Mo Chen,James L. Manley +1 more
TL;DR: Great progress has been made by studying individual transcripts and through genome-wide approaches, which together provide a better picture of the mechanistic regulation of alternative pre-mRNA splicing.
Journal ArticleDOI
The hnRNP family: insights into their role in health and disease
TL;DR: This review will discuss the current knowledge about the different hnRNP family members, focusing on their structural and functional divergence, and highlight their involvement in neurodegenerative diseases and cancer, and the potential to develop RNA-based therapies.
References
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Journal ArticleDOI
hnRNP complexes: composition, structure, and function.
TL;DR: Heterogeneous nuclear ribonucleoproteins are predominantly nuclear RNA-binding proteins that form complexes with RNA polymerase II transcripts that function in a staggering array of cellular activities, ranging from transcription and pre-mRNA processing in the nucleus to cytoplasmic mRNA translation and turnover.
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Transport of Proteins and RNAs in and out of the Nucleus
Sara Nakielny,Gideon Dreyfuss +1 more
TL;DR: It is hoped colleagues will accept the sincere apologies for omitting, due to space limitations, many citations of very important contributions to the field.
Journal ArticleDOI
mRNA Silencing in Erythroid Differentiation: hnRNP K and hnRNP E1 Regulate 15-Lipoxygenase Translation from the 3′ End
Dirk H. Ostareck,Antje Ostareck-Lederer,Matthias Wilm,Bernd J. Thiele,Matthias Mann,Matthias W. Hentze +5 more
TL;DR: The purified two proteins from rabbit reticulocytes that specifically mediate LOX silencing are identified as hnRNPs K and E1 and suggest a specific cytoplasmic function for hn RNPs as translational regulatory proteins.
Journal ArticleDOI
Engineering unnatural nucleotide specificity for Rous sarcoma virus tyrosine kinase to uniquely label its direct substrates
TL;DR: The development of a protein engineering-based method to identify the direct substrates of the prototypical protein tyrosine kinase v-Src, which controls fibroblast transformation by the Rous sarcoma virus, is described.
Journal ArticleDOI
An RNA-binding protein associated with Src through its SH2 and SH3 domains in mitosis
TL;DR: It is reported that a 68K protein (p68) becomes tyrosine-phosphorylated and physically associates with Src during mitosis in mouse fibroblasts, raising the intriguing possibility that c-Src may regulate the processing, trafficking or translation of RNA in a cell-cycle-dependent manner.