hnRNP L is required for the translation mediated by HCV IRES

Hwang, Byounghoon; Lim, Jong In; Hahm, Bumsuk; Jang, Sung Key; Lee, Seong-Wook

doi:10.1016/j.bbrc.2008.11.091

Cited by 51 publications

(35 citation statements)

References 32 publications

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“…(37). However, in our study hnRNP L had little effect on the translation of a minigenome reporter containing both HCV UTRs, indicating that it is not essential for HCV IRES-dependent translation initiation (Fig.…”

Section: Discussionmentioning

confidence: 54%

hnRNP L and NF90 Interact with Hepatitis C Virus 5′-Terminal Untranslated RNA and Promote Efficient Replication

Masaki

Shimakami

et al. 2014

J Virol

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The 5=-terminal sequence of the hepatitis C virus (HCV) positive-strand RNA genome is essential for viral replication. Critical host factors, including a miR-122/Ago2 complex and poly(rC)-binding protein 2 (PCBP2), associate with this RNA segment. We used a biotinylated RNA pulldown approach to isolate host factors binding to the HCV 5= terminal 47 nucleotides and, in addition to Ago2 and PCBP2, identified several novel proteins, including IGF2BP1, hnRNP L, DHX9, ADAR1, and NF90 (ILF3). PCBP2, IGF2BP1, and hnRNP L bound single-stranded RNA, while DHX9, ADAR1, and NF90 bound a cognate double-stranded RNA bait. PCBP2, IGF2BP1, and hnRNP L binding were blocked by preannealing the single-stranded RNA bait with miR-122, indicating that they bind the RNA in competition with miR-122. However, IGF2BP1 binding was also inhibited by high concentrations of heparin, suggesting that it bound the bait nonspecifically. Among these proteins, small interfering RNA-mediated depletion of hnRNP L and NF90 significantly impaired viral replication and reduced infectious virus yields without substantially affecting HCV internal ribosome entry site-mediated translation. hnRNP L and NF90 were found to associate with HCV RNA in infected cells and to coimmunoprecipitate with NS5A in an RNA-dependent manner. Both also associate with detergent-resistant membranes where viral replication complexes reside. We conclude that hnRNP and NF90 are important host factors for HCV replication, at least in cultured cells, and may be present in the replication complex. IMPORTANCEAlthough HCV replication has been intensively studied in many laboratories, many aspects of the viral life cycle remain obscure. Here, we use a novel RNA pulldown strategy coupled with mass spectrometry to identify host cell proteins that interact functionally with regulatory RNA elements located at the extreme 5= end of the positive-strand RNA genome. We identify two, primarily nuclear RNA-binding proteins, hnRNP L and NF90, with previously unrecognized proviral roles in HCV replication. The data presented add to current understanding of the replication cycle of this pathogenic human virus.

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Section: Discussionmentioning

confidence: 54%

hnRNP L and NF90 Interact with Hepatitis C Virus 5′-Terminal Untranslated RNA and Promote Efficient Replication

Masaki

Shimakami

et al. 2014

J Virol

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“…2c). Few proteins have been proposed to function as ITAFs in hepatitis C virus translation [83,96,97]. Type 4 IRES within the intergenic region of cricket paralysis virus (CrPV) mimics a tRNA directly recruiting 40S or 80S ribosome without initiation factors and initiator tRNA, and initiates translation at a non-AUG codon from the ribosomal A-site [98][99][100][101] (Fig.…”

Section: Internal Initiation Mechanisms In Eukaryamentioning

confidence: 99%

Translation initiation: variations in the mechanism can be anticipated

Malys

McCarthy

2010

Cell. Mol. Life Sci.

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Translation initiation is a critical step in protein synthesis. Previously, two major mechanisms of initiation were considered as essential: prokaryotic, based on SD interaction; and eukaryotic, requiring cap structure and ribosomal scanning. Although discovered decades ago, cap-independent translation has recently been acknowledged as a widely spread mechanism in viruses, which may take place in some cellular mRNA translations. Moreover, it has become evident that translation can be initiated on the leaderless mRNA in all three domains of life. New findings demonstrate that other distinguishable types of initiation exist, including SD-independent in Bacteria and Archaea, and various modifications of 5' end-dependent and internal initiation mechanisms in Eukarya. Since translation initiation has developed through the loss, acquisition, and modification of functional elements, all of which have been elevated by competition with viral translation in a large number of organisms of different complexity, more variation in initiation mechanisms can be anticipated.

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“…hnRNP L is an abundant and multifunctional protein that shuttles between the nucleus and cytoplasm. It mediates selective exon inclusion during alternative splicing (3), facilitates polyadenylation (4), assists export of intronless gene mRNA (5), promotes internal ribosomal entry site-dependent translation (6,7), and regulates mRNA stability (8,9). hnRNP L interacts with other hnRNPs, including hnRNP A2 (10), E2, I, and K (11).…”

Section: Heterogeneous Nuclear Ribonucleoproteins (Hnrnps)mentioning

confidence: 99%

Crystal Structures and RNA-binding Properties of the RNA Recognition Motifs of Heterogeneous Nuclear Ribonucleoprotein L

Zhang

Zeng

Liu

et al. 2013

Journal of Biological Chemistry

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Background: hnRNP L is a multifunctional RNA-binding protein implicated in alternative splicing regulation, etc. Results: RRM1 and RRM34 of hnRNP L adopt nearly typical RRM topology and use ␤-sheets to bind RNA. Conclusion: hnRNP L RRM34 facilitates the target RNA with appropriate in-between distance to form a loop. Significance: RNA looping suggests a general mechanism for alternative splicing regulators possessing position-dependent dual roles.

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hnRNP L is required for the translation mediated by HCV IRES

Cited by 51 publications

References 32 publications

hnRNP L and NF90 Interact with Hepatitis C Virus 5′-Terminal Untranslated RNA and Promote Efficient Replication

hnRNP L and NF90 Interact with Hepatitis C Virus 5′-Terminal Untranslated RNA and Promote Efficient Replication

Translation initiation: variations in the mechanism can be anticipated

Crystal Structures and RNA-binding Properties of the RNA Recognition Motifs of Heterogeneous Nuclear Ribonucleoprotein L

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