mRNA Nuclear Export in Yeast

Niño, Carlos A Martínez; Hérissant, Lucas; Babour, Anna; Dargemont, Catherine

doi:10.1021/cr400002g

Cited by 57 publications

(57 citation statements)

References 310 publications

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“…For example, in the case of mRNA, only select Pol II transcripts are matured and selected for export by the incorporation of Mex67 into the mRNP [2,4]. It is known that Mex67 binds along the length of the mRNA with no apparent sequence specificity [14 ,15 ] and it is likely that interactions with other RBPs (e.g.…”

Section: Determinants Of Rnp Compositionmentioning

confidence: 99%

“…Ribonucleoprotein particles (RNPs) are assembled and matured in the nucleus through a series of events that begin with transcription and often end with an RNP being exported to the cytoplasm via a nuclear pore complex (NPC) [1,2]. Maturation is driven by transient interactions with RNA binding proteins (RBPs), which facilitate individual biogenesis steps that are unique to the type of RNA [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Emerging properties of nuclear RNP biogenesis and export

Oeffinger¹,

Montpetit²

2015

Current Opinion in Cell Biology

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Section: Determinants Of Rnp Compositionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Emerging properties of nuclear RNP biogenesis and export

Oeffinger¹,

Montpetit²

2015

Current Opinion in Cell Biology

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“…A series of molecular events are required for facilitating mRNP translocation through NPCs and executing directional release of mRNPs into the cytoplasm. Detailed reviews have been published recently outlining the current understanding of these mechanisms (4,(20)(21)(22). However, additional work has been required to resolve whether Nup export functions are distinct from or connected with roles for Nups in transcription and genome organization.…”

Section: Defining the Npc Composition And Roles In Rna Exportmentioning

confidence: 99%

From Hypothesis to Mechanism: Uncovering Nuclear Pore Complex Links to Gene Expression

Burns

Wente

2014

Molecular and Cellular Biology

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The gene gating hypothesis put forth by Blobel in 1985 was an alluring proposal outlining functions for the nuclear pore complex (NPC) in transcription and nuclear architecture. Over the past several decades, collective studies have unveiled a full catalog of nucleoporins (Nups) that comprise the NPC, structural arrangements of Nups in the nuclear pore, and mechanisms of nucleocytoplasmic transport. With this foundation, investigations of the gene gating hypothesis have now become possible. Studies of several model organisms provide credence for Nup functions in transcription, mRNA export, and genome organization. Surprisingly, Nups are not only involved in transcriptional events that occur at the nuclear periphery, but there are also novel roles for dynamic Nups within the nucleoplasmic compartment. Several tenants of the original gene gating hypothesis have yet to be addressed. Knowledge of whether the NPC impacts the organization of the genome to control subsets of genes is limited, and the cooperating molecular machinery or specific genomic anchoring sequences are not fully resolved. This minireview summarizes the current evidence for gene gating in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mammalian model systems. These examples highlight new and unpredicted mechanisms for Nup impacts on transcription and questions that are left to be explored.

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“…In the present view, the mRNA undergoes a handover mediated by protein interactions from UAP56 to ALY, a TAP-NXT adaptor protein. UAP56 copurifies with the THO/ TREX complex, a multimeric complex involved in the coupling of transcription and RNA export (8). Finally, the TAP-NXT dimer is responsible for the interaction with the FG-containing nucleoporins and catalyzes export of the bound RNA (summarized in references 9 to 15).…”

mentioning

confidence: 99%

ORF57 Overcomes the Detrimental Sequence Bias of Kaposi's Sarcoma-Associated Herpesvirus Lytic Genes

Vogt¹,

Hackmann²,

Rabner³

et al. 2015

J Virol

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Kaposi's sarcoma-associated herpesvirus (KSHV) encodes ORF57, which enhances the expression of intronless KSHV genes on multiple posttranscriptional levels. However, it remains elusive how ORF57 recognizes viral RNAs. Here, we demonstrate that ORF57 also increases the expression of the multiple intron-containing K15 gene. The nucleotide bias of the K15 cDNA revealed an unusual high AT content. Thus, we optimized the K15 cDNA by raising the frequency of GC nucleotides, yielding an ORF57-independent version. To further prove the importance of the sequence bias of ORF57-dependent RNAs, we grouped KSHV mRNAs according to their AT content and found a correlation between AT-richness and ORF57 dependency. More importantly, latent genes, which have to be expressed in the absence of ORF57, have a low AT content and are indeed ORF57 independent. The nucleotide composition of K15 resembles that of HIV gag, which cannot be expressed unless RNA export is facilitated by the HIV Rev protein. Interestingly, ORF57 can partially rescue HIV Gag expression. Thus, the KSHV target RNAs of ORF57 and HIV gag RNA may share certain motifs based on the nucleotide bias. A bioinformatic comparison between wild-type and sequenceoptimized K15 revealed a higher density for hnRNP-binding motifs in the former. We speculate that binding of particular hnRNPs to KSHV lytic transcripts is the prerequisite for ORF57 to enhance their expression. IMPORTANCEThe mostly intronless genes of KSHV are only expressed in the presence of the viral regulator protein ORF57, but how ORF57 recognizes viral RNAs remains elusive. We focused on the multiple intron-containing KSHV gene K15 and revealed that its expression is also increased by ORF57. Moreover, sequences in the K15 cDNA mediate this enhancement. The quest for a target sequence or a response element for ORF57 in the lytic genes was not successful. Instead, we found the nucleotide bias to be the critical determinant of ORF57 dependency. Based on the fact that ORF57 has only a weak affinity for nucleic acids, we speculate that a cellular RNA-binding protein provides the sequence preference for ORF57. This study provides evidence that herpesviral RNA regulator proteins use the sequence bias of lytic genes and the resulting composition of the viral mRNP to distinguish between viral and cellular mRNAs. K aposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus that was identified in KS tissues from AIDS patients (1). It is also associated with two lymphoproliferative disorders, the primary effusion lymphoma and the plasma cell variant of multicentric Castleman's disease. KSHVassociated malignancies are rare in immunocompetent people but more common in the context of immunosuppression, especially in HIV patients or transplant recipients. The viral life cycle is divided into a latent and a lytic phase. In contrast to other herpesviruses, tumorigenesis is also a consequence of the lytic cycle (2-5).Herpesviruses replicate in the nucleus, and viral gene expression is dependent on the host ...

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mRNA Nuclear Export in Yeast

Cited by 57 publications

References 310 publications

Emerging properties of nuclear RNP biogenesis and export

Emerging properties of nuclear RNP biogenesis and export

From Hypothesis to Mechanism: Uncovering Nuclear Pore Complex Links to Gene Expression

ORF57 Overcomes the Detrimental Sequence Bias of Kaposi's Sarcoma-Associated Herpesvirus Lytic Genes

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