"Friedrich Miescher Prize Awardee Lecture Review"¶A conserved family of nuclear export receptors mediates the exit of messenger RNA to the cytoplasm

2001 ◽  
Vol 58 (8) ◽  
pp. 1105-1112 ◽  
Author(s):  
E. Izaurralde
Keyword(s):  
Nuclear Export ◽  
Messenger Rna ◽  
Export Receptors

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

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.

scholarly journals Nuclear Export of Messenger RNA

Genes ◽  
2015 ◽  
Vol 6 (2) ◽  
pp. 163-184 ◽  
Author(s):  
Jun Katahira
Keyword(s):  
Nuclear Export ◽  
Messenger Rna

scholarly journals SR proteins: To shuttle or not to shuttle, that is the question

2017 ◽  
Vol 216 (7) ◽  
pp. 1875-1877 ◽  
Author(s):  
Marie-Louise Hammarskjold ◽  
David Rekosh
Keyword(s):  
Nuclear Export ◽  
Messenger Rna ◽  
Sr Proteins ◽  
P19 Cells ◽  
Differentiated Cells ◽  
Cell Biol

Serine- and arginine-rich proteins play important roles in splicing, nuclear export, and translation. In this issue, Botti et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610051) show that SRSF2 and SRSF5, previously thought to be nuclear, shuttle with messenger RNA to the cytoplasm in pluripotent P19 cells, but not in differentiated cells.

scholarly journals The Nuclear Export Receptors TbMex67 and TbMtr2 Are Required for Ribosome Biogenesis in Trypanosoma brucei

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Constance Rink ◽  
Martin Ciganda ◽  
Noreen Williams
Keyword(s):  
Trypanosoma Brucei ◽  
Nuclear Export ◽  
Ribosome Biogenesis ◽  
Biological Process ◽  
Large Subunit ◽  
Critical Role ◽  
Ribosomal Subunits ◽  
Content Type ◽  
Protein Components ◽  
Export Receptors

ABSTRACT Ribosomal maturation is a complex and highly conserved biological process involving migration of a continuously changing RNP across multiple cellular compartments. A critical point in this process is the translocation of individual ribosomal subunits (60S and 40S) from the nucleus to the cytoplasm, and a number of export factors participate in this process. In this study, we characterize the functional role of the auxiliary export receptors TbMex67 and TbMtr2 in ribosome biogenesis in the parasite Trypanosoma brucei. We demonstrate that depletion of each of these proteins dramatically impacts the steady-state levels of other proteins involved in ribosome biogenesis, including the trypanosome-specific factors P34 and P37. In addition, we observe that the loss of TbMex67 or TbMtr2 leads to aberrant ribosome formation, rRNA processing, and polysome formation. Although the TbMex67-TbMtr2 heterodimer is structurally distinct from Mex67-Mtr2 complexes previously studied, our data show that they retain a conserved function in ribosome biogenesis. IMPORTANCE The nuclear export of ribosomal subunits (60S and 40S) depends in part on the activity of the essential auxiliary export receptors TbMtr2 and TbMex67. When these proteins are individually depleted from the medically and agriculturally significant parasite Trypanosoma brucei, distinct alterations in the processing of the rRNAs of the large subunit (60S) are observed as well as aberrations in the assembly of functional ribosomes (polysomes). We also established that TbMex67 and TbMtr2 interact directly or indirectly with the protein components of the 5S RNP, including the trypanosome-specific P34/P37. The critical role that TbMex67 and TbMtr2 play in this essential biological process together with their parasite-specific interactions may provide new therapeutic targets against this important parasite.

The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans

Nature ◽  
2000 ◽  
Vol 407 (6802) ◽  
pp. 401-405 ◽  
Author(s):  
Zhaolan Zhou ◽  
Ming-juan Luo ◽  
Katja Straesser ◽  
Jun Katahira ◽  
Ed Hurt ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Rna Splicing ◽  
Messenger Rna

scholarly journals A conserved CCCH-type zinc finger protein regulates mRNA nuclear adenylation and export

2009 ◽  
Vol 185 (2) ◽  
pp. 265-277 ◽  
Author(s):  
Jessica A. Hurt ◽  
Robert A. Obar ◽  
Bo Zhai ◽  
Natalie G. Farny ◽  
Steven P. Gygi ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Zinc Finger Protein ◽  
Liquid Chromatography Mass Spectrometry ◽  
Functional Conservation ◽  
Finger Protein ◽  
Interfering Rna ◽  
Processing Steps ◽  
Prior Processing

Coupling of messenger RNA (mRNA) nuclear export with prior processing steps aids in the fidelity and efficiency of mRNA transport to the cytoplasm. In this study, we show that the processes of export and polyadenylation are coupled via the Drosophila melanogaster CCCH-type zinc finger protein CG6694/dZC3H3 through both physical and functional interactions. We show that depletion of dZC3H3 from S2R+ cells results in transcript hyperadenylation. Using targeted coimmunoprecipitation and liquid chromatography mass spectrometry (MS)/MS techniques, we characterize interactions of known components of the mRNA nuclear export and polyadenylation machineries with dZC3H3. Furthermore, we demonstrate the functional conservation of this factor, as depletion of its human homologue ZC3H3 by small interfering RNA results in an mRNA export defect in human cells as well. Nuclear polyadenylated (poly(A)) RNA in ZC3H3-depleted cells is sequestered in foci removed from SC35-containing speckles, indicating a shift from the normal subnuclear distribution of poly(A) RNA. Our data suggest a model wherein ZC3H3 interfaces between the polyadenylation machinery, newly poly(A) mRNAs, and factors for transcript export.

scholarly journals Dual action of epidermal growth factor: extracellular signal-stimulated nuclear–cytoplasmic export and coordinated translation of selected messenger RNA

2010 ◽  
Vol 188 (3) ◽  
pp. 325-333 ◽  
Author(s):  
Nien-Pei Tsai ◽  
Ya-Lun Lin ◽  
Yao-Chen Tsui ◽  
Li-Na Wei
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Rna Binding ◽  
Tyrosine Phosphatase ◽  
Growth Factor Receptor ◽  
Dual Action ◽  
Epidermal Growth ◽  
Specific Mrna

We report the first example of a coordinated dual action of epidermal growth factor (EGF) in stimulating the nuclear–cytoplasmic export and translation of a select messenger RNA (mRNA). The effect of EGF is mediated by the RNA-binding protein Grb7 (growth factor receptor–bound protein 7), which serves as an adaptor for a specific mRNA–protein export complex and a translational regulator. Using the κ–opioid receptor (OR [KOR]) as a model, we demonstrate that EGF activates nuclear SHP-2 (Src homology region 2–containing tyrosine phosphatase), which dephosphorylates Grb7 in the nucleus. Hypophosphorylated Grb7 binds to the KOR mRNA and recruits the Hu antigen R–exportin-1 (CRM1) complex to form a nuclear–cytoplasmic export complex that exports KOR mRNA. EGF also activates focal adhesion kinase in the cytoplasm to rephosphorylate Grb7, releasing KOR mRNA for active translation. In summary, this study uncovers a coordinated, dual activity of EGF in facilitating nuclear export of a specific mRNA–protein complex as well as translational activation of the exported mRNA.

scholarly journals The Great Escape: mRNA Export through the Nuclear Pore Complex

2021 ◽  
Vol 22 (21) ◽  
pp. 11767
Author(s):  
Paola De Magistris
Keyword(s):  
Conformational Changes ◽  
Nuclear Pore Complex ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Mrna Export ◽  
Protein Translation ◽  
Nuclear Pore ◽  
Body Of Knowledge ◽  
Transport Receptors ◽  
Basic Characteristics

Nuclear export of messenger RNA (mRNA) through the nuclear pore complex (NPC) is an indispensable step to ensure protein translation in the cytoplasm of eukaryotic cells. mRNA is not translocated on its own, but it forms ribonuclear particles (mRNPs) in association with proteins that are crucial for its metabolism, some of which; like Mex67/MTR2-NXF1/NXT1; are key players for its translocation to the cytoplasm. In this review, I will summarize our current body of knowledge on the basic characteristics of mRNA export through the NPC. To be granted passage, the mRNP cargo needs to bind transport receptors, which facilitate the nuclear export. During NPC transport, mRNPs undergo compositional and conformational changes. The interactions between mRNP and the central channel of NPC are described; together with the multiple quality control steps that mRNPs undergo at the different rings of the NPC to ensure only proper export of mature transcripts to the cytoplasm. I conclude by mentioning new opportunities that arise from bottom up approaches for a mechanistic understanding of nuclear export.

scholarly journals Understanding COVID-19 Pathogenesis: A Drug-Repurposing Effort to Disrupt Nsp-1 Binding to Export Machinery Receptor Complex

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1634
Author(s):  
Sona Vasudevan ◽  
James N. Baraniuk
Keyword(s):  
Structural Analysis ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Drug Repurposing ◽  
Nuclear Pore ◽  
Receptor Complex ◽  
Structural Protein ◽  
Gonadotropin Secretion ◽  
Approved Drugs ◽  
Nuclear Rna Export

Non-structural protein 1 (Nsp1) is a virulence factor found in all beta coronaviruses (b-CoVs). Recent studies have shown that Nsp1 of SARS-CoV-2 virus interacts with the nuclear export receptor complex, which includes nuclear RNA export factor 1 (NXF1) and nuclear transport factor 2-like export factor 1 (NXT1). The NXF1–NXT1 complex plays a crucial role in the transport of host messenger RNA (mRNA). Nsp1 interferes with the proper binding of NXF1 to mRNA export adaptors and its docking to the nuclear pore complex. We propose that drugs targeting the binding surface between Nsp1 and NXF1–NXT1 may be a useful strategy to restore host antiviral gene expression. Exploring this strategy forms the main goals of this paper. Crystal structures of Nsp1 and the heterodimer of NXF1–NXT1 have been determined. We modeled the docking of Nsp1 to the NXF1–NXT1 complex, and discovered repurposed drugs that may interfere with this binding. To our knowledge, this is the first attempt at drug-repurposing of this complex. We used structural analysis to screen 1993 FDA-approved drugs for docking to the NXF1–NXT1 complex. The top hit was ganirelix, with a docking score of −14.49. Ganirelix competitively antagonizes the gonadotropin releasing hormone receptor (GNRHR) on pituitary gonadotrophs, and induces rapid, reversible suppression of gonadotropin secretion. The conformations of Nsp1 and GNRHR make it unlikely that they interact with each other. Additional drug leads were inferred from the structural analysis of this complex, which are discussed in the paper. These drugs offer several options for therapeutically blocking Nsp1 binding to NFX1–NXT1, which may normalize nuclear export in COVID-19 infection.

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