The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophila

Büssing, Ingo; Yang, Jr-Shiuan; Lai, Eric C.; Großhans, Helge

doi:10.1038/emboj.2010.82

Cited by 76 publications

(68 citation statements)

References 52 publications

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“…Previous studies showed that Exportin-1, an essential transport factor for certain proteins and RNAs, supports pri-miRNA processing in Caenorhabditis elegans and Drosophila, as well as shuttling of mature miRNA from the cytoplasm to the nucleus (28,41,42). Recently, we showed that Exportin-1 is involved in the nuclear export of a group of mammalian (m 7 G)-capped pre-miRNAs in proliferating cells (27).…”

Section: Exportin-1 Is Required For Processing Of Quiescence-induced mentioning

confidence: 99%

“…Exportin-1, the major factor responsible for the export of proteins from the nucleus, is also involved in the export of certain RNAs such as ribosomal RNAs, snRNAs, and mRNAs encoding some proteins involved in cell-cycle regulation (28,52). Previous studies in C. elegans and Drosophila showed that Exportin-1 is involved in pri-miRNA processing and biogenesis (41). Our findings demonstrate that Exportin-1 is also involved in the biogenesis of specific miRNAs in proliferating mammalian cells and that this activity is enhanced during quiescence.…”

Section: Exportin-1-dependent Mirna Biogenesis Occurs During Cellularmentioning

confidence: 99%

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An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

Martínez

Hayes

Barr

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The reversible state of proliferative arrest known as "cellular quiescence" plays an important role in tissue homeostasis and stem cell biology. By analyzing the expression of miRNAs and miRNAprocessing factors during quiescence in primary human fibroblasts, we identified a group of miRNAs that are induced during quiescence despite markedly reduced expression of Exportin-5, a protein required for canonical miRNA biogenesis. The biogenesis of these quiescence-induced miRNAs is independent of Exportin-5 and depends instead on Exportin-1. Moreover, these quiescence-induced primary miRNAs (pri-miRNAs) are modified with a 2,2,7-trimethylguanosine (TMG)-cap, which is known to bind Exportin-1, and knockdown of Exportin-1 or trimethylguanosine synthase 1, responsible for (TMG)-capping, inhibits their biogenesis. Surprisingly, in quiescent cells Exportin-1-dependent pri-miR-34a is present in the cytoplasm together with a small isoform of Drosha, implying the existence of a different miRNA processing pathway in these cells. Our findings suggest that during quiescence the canonical miRNA biogenesis pathway is down-regulated and specific miRNAs are generated by an alternative pathway to regulate genes involved in cellular growth arrest.M ost metazoan cells enter a reversible cell-cycle arrest known as "cellular quiescence" when they are exposed to antimitogenic signals or an environment unfavorable for proliferation (1, 2). In mammalian cells, quiescence (also known as "G 0 arrest") is characterized by reduced DNA replication, altered metabolism, increased autophagy, and increased expression of cyclin-dependent kinase inhibitors such as p27 Kip1 (3,4). In vitro, quiescence can be induced in primary cells by serum starvation, contact inhibition, and loss of adhesion to a substrate (5). Quiescence is involved in important cellular processes, including the balance between differentiation and self-renewal in different types of stem cells, and dysregulation of quiescence could favor carcinogenesis. However, the molecular mechanisms that regulate quiescence are poorly understood (6). miRNAs are small, noncoding RNAs ∼22-nt long that regulate the expression of protein-coding genes by base-pairing with the 3′ UTR of mRNAs, repressing the translation and/or inducing the degradation of the target mRNA (7,8). In canonical miRNA biogenesis in mammalian cells, miRNAs are transcribed by RNA polymerase II to produce 7-methylguanosine (m 7 G)-capped primary miRNAs (pri-miRNAs) containing one or more bulged hairpin structures that are recognized by the nuclear microprocessor, which consists of the RNase III enzyme Drosha and the dsRNA-binding protein DGCR8 (DiGeorge syndrome critical region gene 8) (9-12). Specific cleavage of the pri-miRNA by the nuclear microprocessor generates an ∼70-nt stem-loop structure known as the "precursor miRNA" (pre-miRNA), which is recognized and transported to the cytoplasm by 10,11,13). Subsequently, pre-miRNA is cleaved by the cytoplasmic RNase III enzyme Dicer (14-17), generating a double-stranded mature mi...

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Section: Exportin-1 Is Required For Processing Of Quiescence-induced mentioning

confidence: 99%

Section: Exportin-1-dependent Mirna Biogenesis Occurs During Cellularmentioning

confidence: 99%

An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

Martínez

Hayes

Barr

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The best-characterized miRNA in C. elegans is let-7, which controls developmental timing. Mutations in let-7 block the transition from late larval to adult cell fates, in particular by fusion of seam cells, and animals often die from a bursting vulvae phenotype (Bussing et al 2010). Knockdown of XPO-1, or inhibition of the cap-binding complex (consisting of NCBP-1 and NCBP-2), which acts as an adaptor for XPO-1, causes similar developmental defects as well as a 50% reduction in mature let-7 miRNA, arguing that XPO-1 is likely the transport receptor of pre-miRNAs in C. elegans (Bussing et al 2010).…”

Section: Nuclear Localization and Nuclear Export Signalsmentioning

confidence: 99%

Cell Biology of theCaenorhabditis elegansNucleus

Cohen-Fix

Askjaer

2017

Genetics

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Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology.KEYWORDS Caenorhabditis elegans; chromatin; gene expression; lamin; LEM-domain proteins; LINC; P granule; nuclear pore complex; nuclear envelope; nucleocytoplasmic transport; nucleolus; WormBook TABLE OF CONTENTSAbstract 25 C. elegans as a model system to study cell biology of the nucleus 26 Structural components of the nucleus 27

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“…Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.2265710. miRNA biogenesis pathways has been recently indicated in Arabidopsis, and this has been extended to RNA silencing in animals (Gregory et al 2008;Kim et al 2008;Laubinger et al 2008;Gruber et al 2009;Sabin et al 2009;Büssing et al 2010). Connecting these two processes permits more robust and accurate regulation of gene expression, and further inquiry into the crosstalk is expected to reveal additional roles.…”

Section: Introductionmentioning

confidence: 99%

Characterization of EMU, the Arabidopsis homolog of the yeast THO complex member HPR1

Furumizu¹,

Tsukaya²,

Komeda³

2010

RNA

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Diverse and precise control is essential for eukaryotic gene expression. This is accomplished through the recruitment of a myriad of proteins to a nascent messenger RNA (mRNA) to mediate modifications, such as capping, splicing, 39-end processing, and export. Despite being important for every cell, however, the mechanism by which the formation of diverse messenger ribonucleoprotein (mRNP) particles contributes to maintaining intricate systems in the multicellular organism remains incompletely defined. We identified and characterized a mutant gene named erecta mRNA under-expressed (emu) that leads to the defective mRNA accumulation of ERECTA, a developmental regulator in the model plant Arabidopsis thaliana. EMU encodes a protein homologous to a component of the THO complex that is required for the generation of functional mRNPs. Further analysis suggested that EMU is genetically associated with SERRATE, HYPONASTIC LEAVES1, and ARGONAUTE1, which are required for proper RNA maturation or action. Furthermore, mutations in another THO-related gene led to embryonic lethality. These findings support the presence and importance of the THO-related complex in plants as well as yeast and vertebrates.

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The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophila

Cited by 76 publications

References 52 publications

An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

Cell Biology of theCaenorhabditis elegansNucleus

Characterization of EMU, the Arabidopsis homolog of the yeast THO complex member HPR1

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