Mammalian GW220/TNGW1 is essential for the formation of GW/P bodies containing miRISC

The microRNA (miRNA)-induced silencing complex (miRISC) controls gene expression by a posttranscriptional mechanism involving translational repression and/or promoting messenger RNA (mRNA) deadenylation and degradation. The GW182/TNRC6 (GW) family proteins are core components of the miRISC and are essential for miRNA function. We show that mammalian GW proteins have distinctive functions in the miRNA pathway, with GW220/TNGW1 being essential for the formation of GW/P bodies containing the miRISC. miRISC aggregation and formation of GW/P bodies sequestered and stabilized translationally repressed target mRNA. Depletion of GW220 led to the loss of GW/P bodies and destabilization of miRNA-targeted mRNA. These findings support a model in which the cellular localization of the miRISC regulates the fate of the target mRNA.

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P-bodies and the miRNA pathway regulate translational repression of bicoid mRNA during Drosophila melanogaster oogenesis

10.1101/283630 ◽

2018 ◽

Author(s):

John M. McLaughlin ◽

Daniel F.Q. Smith ◽

Irina E. Catrina ◽

Diana P. Bratu

Keyword(s):

Drosophila Melanogaster ◽

Small Rna ◽

Translational Regulation ◽

Translational Repression ◽

Temporal Regulation ◽

P Bodies ◽

Maternal Transcripts ◽

Spatio Temporal ◽

Mirna Pathway ◽

Rna Pathways

ABSTRACTEmbryonic axis patterning in Drosophila melanogaster is partly achieved by mRNAs that are maternally localized to the oocyte; the spatio-temporal regulation of these transcripts’ stability and translation is a characteristic feature of oogenesis. While protein regulatory factors are necessary for the translational regulation of some maternal transcripts (e.g. oskar and gurken), small RNA pathways are also known to regulate mRNA stability and translation in eukaryotes. MicroRNAs (miRNAs) are small RNA regulators of gene expression, widely conserved throughout eukaryotic genomes and essential for animal development. The main D. melanogaster anterior determinant, bicoid, is maternally transcribed, but it is not translated until early embryogenesis. We investigated the possibility that its translational repression during oogenesis is mediated by miRNA activity. We found that the bicoid 3’UTR contains a highly conserved, predicted binding site for miR-305. Our studies reveal that miR-305 regulates the translation of a reporter gene containing the bicoid 3’UTR in cell culture, and that miR-305 only partially contributes to bicoid mRNA translational repression during oogenesis. We also found that Processing bodies (P-bodies) in the egg chamber may play a role in stabilizing bicoid and other maternal transcripts. Here, we offer insights into the possible role of P-bodies and the miRNA pathway in the translational repression of bicoid mRNA during oogenesis.

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Microtubule disruption targets HIF-1α mRNA to cytoplasmic P-bodies for translational repression

The Journal of Cell Biology ◽

10.1083/jcb.201004145 ◽

2011 ◽

Vol 192 (1) ◽

pp. 83-99 ◽

Cited By ~ 66

Author(s):

Marisa Carbonaro ◽

Aurora O'Brate ◽

Paraskevi Giannakakou

Keyword(s):

Solid Tumors ◽

Cell Biology ◽

Messenger Rna ◽

Hypoxia Inducible Factor ◽

Translational Repression ◽

P Bodies ◽

Argonaute 2 ◽

Microtubule Disruption ◽

Significant Enrichment ◽

Body Component

The hypoxia inducible factor 1α (HIF-1α) is overexpressed in solid tumors, driving tumor angiogenesis and survival. However, the mechanisms regulating HIF-1α expression in solid tumors are not fully understood. In this study, we find that microtubule integrity and dynamics are intricately involved in orchestrating HIF-1α translation. HIF-1α messenger RNA (mRNA) traffics on dynamic microtubules when it is actively translated. Microtubule perturbation by taxol (TX) and other microtubule-targeting drugs stalls HIF-1α mRNA transport and releases it from polysomes, suppressing its translation. Immunoprecipitation of the P-body component Argonaute 2 (Ago2) after microtubule disruption shows significant enrichment of HIF-1α mRNAs and HIF-targeting microRNAs (miRNAs). Inhibition of HIF-repressing miRNAs or Ago2 knockdown abrogates TX’s ability to suppress HIF-1α translation. Interestingly, microtubule repolymerization after nocodazole washout allows HIF-1α mRNA to reenter active translation, suggesting that microtubule dynamics exert tight yet reversible control over HIF-1α translation. Collectively, we provide evidence for a new mechanism of microtubule-dependent HIF-1α translation with important implications for cell biology.

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How do microRNAs regulate gene expression?

Biochemical Society Transactions ◽

10.1042/bst0361224 ◽

2008 ◽

Vol 36 (6) ◽

pp. 1224-1231 ◽

Cited By ~ 166

Author(s):

Ian G. Cannell ◽

Yi Wen Kong ◽

Martin Bushell

Keyword(s):

Gene Expression ◽

Untranslated Region ◽

Protein Production ◽

Translational Repression ◽

Regulate Gene Expression ◽

Target Mrna ◽

Target Mrnas ◽

Non Coding Rnas ◽

Regulate Gene

miRNAs (microRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally. They generally bind to the 3′-UTR (untranslated region) of their target mRNAs and repress protein production by destabilizing the mRNA and translational silencing. The exact mechanism of miRNA-mediated translational repression is yet to be fully determined, but recent data from our laboratory have shown that the stage of translation which is inhibited by miRNAs is dependent upon the promoter used for transcribing the target mRNA. This review focuses on understanding how miRNA repression is operating in light of these findings and the questions that still remain.

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Yeast mRNA localization: protein asymmetry, organelle localization and response to stress

Biochemical Society Transactions ◽

10.1042/bst20140086 ◽

2014 ◽

Vol 42 (4) ◽

pp. 1256-1260 ◽

Cited By ~ 9

Author(s):

Mariavittoria Pizzinga ◽

Mark P. Ashe

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Mrna Localization ◽

Translational Repression ◽

Yeast Saccharomyces Cerevisiae ◽

Processing Bodies ◽

Control Of Gene Expression ◽

P Bodies ◽

Response To Stress ◽

Kinetics Of

The localization of mRNA forms a key facet of the post-transcriptional control of gene expression and recent evidence suggests that it may be considerably more widespread than previously anticipated. For example, defined mRNA-containing granules can be associated with translational repression or activation. Furthermore, mRNA P-bodies (processing bodies) harbour much of the mRNA decay machinery and stress granules are thought to play a role in mRNA storage. In the present review, we explore the process of mRNA localization in the yeast Saccharomyces cerevisiae, examining connections between organellar mRNA localization and the response to stress. We also review recent data suggesting that even where there is a global relocalization of mRNA, the specificity and kinetics of this process can be regulated.

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Pat1 proteins: a life in translation, translation repression and mRNA decay

Biochemical Society Transactions ◽

10.1042/bst0381602 ◽

2010 ◽

Vol 38 (6) ◽

pp. 1602-1607 ◽

Cited By ~ 34

Author(s):

Aline Marnef ◽

Nancy Standart

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Mrna Decay ◽

Current Knowledge ◽

Translational Repression ◽

Processing Bodies ◽

P Bodies ◽

Expression Control ◽

Gene Expression Control ◽

Sequential Binding

Pat1 proteins are conserved across eukaryotes. Vertebrates have evolved two Pat1 proteins paralogues, whereas invertebrates and yeast only possess one such protein. Despite their lack of known domains or motifs, Pat1 proteins are involved in several key post-transcriptional mechanisms of gene expression control. In yeast, Pat1p interacts with translating mRNPs (messenger ribonucleoproteins), and is responsible for translational repression and decapping activation, ultimately leading to mRNP degradation. Drosophila HPat and human Pat1b (PatL1) proteins also have conserved roles in the 5′→3′ mRNA decay pathway. Consistent with their functions in silencing gene expression, Pat1 proteins localize to P-bodies (processing bodies) in yeast, Drosophila, Caenorhabditis elegans and human cells. Altogether, Pat1 proteins may act as scaffold proteins allowing the sequential binding of repression and decay factors on mRNPs, eventually leading to their degradation. In the present mini-review, we present the current knowledge on Pat1 proteins in the context of their multiple functions in post-transcriptional control.

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Mucin gene expression in OME: cellular localization

Clinical Otolaryngology ◽

10.1046/j.1365-2273.1998.0138f.x ◽

1998 ◽

Vol 23 (3) ◽

pp. 281-282

Author(s):

Hutton ◽

Guo ◽

Birchall ◽

Pearson

Keyword(s):

Gene Expression ◽

Cellular Localization ◽

Mucin Gene

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Interaction of 7SK with the Smn complex modulates snRNP production

Nature Communications ◽

10.1038/s41467-021-21529-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Changhe Ji ◽

Jakob Bader ◽

Pradhipa Ramanathan ◽

Luisa Hennlein ◽

Felix Meissner ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Fine Tuning ◽

Global Changes ◽

Functional Association ◽

Transcriptional Inhibition ◽

Smn Complex ◽

Core Components

AbstractGene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.

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The crucial roles of N6-methyladenosine (m6A) modification in the carcinogenesis and progression of colorectal cancer

Cell & Bioscience ◽

10.1186/s13578-021-00583-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhihao Fang ◽

Yiqiu Hu ◽

Jinhui Hu ◽

Yanqin Huang ◽

Shu Zheng ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Nuclear Export ◽

Messenger Rna ◽

Regulatory Proteins ◽

Biological Processes ◽

The Past ◽

Common Cancer ◽

Potential Applications ◽

Regulated Gene Expression

AbstractAs the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.

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