5′ Processing of tRNA Precursors Can Be Modulated by the Human La Antigen Phosphoprotein

Fan, Hao; Goodier, John; Chamberlain, Joel R.; Engelke, David R.; Maraia, Richard J

doi:10.1128/mcb.18.6.3201

Cited by 108 publications

(138 citation statements)

References 46 publications

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“…La resides mostly within the nucleus where it is involved in the processing of RNA polymerase III transcripts (Fan et al, 1998;Intine et al, 2003) and acts as a retention factor for mature preexisting mRNAs (Brenet et al, 2005). La can shuttle between the nucleus and cytoplasm upon cellular stress (Baboonian et al, 1989;Bachmann et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

et al. 2008

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The Akt signaling pathway activity increases as normal tissue progresses to malignant transformation, and regulates the translation of specific messenger RNAs (mRNAs) through multiple mechanisms. We have identified one such mechanism of Akt-dependent translation control as involving the lupus autoantigen La. La is an RNA-associated protein that contains multiple trafficking elements to support the interaction with RNAs in different subcellular locations. We show here that the La protein is a direct target of the serine/threonine protein kinase Akt on threonine 301, and La nuclear export in mouse glial progenitors, as well as its association with polysomes is modulated by Akt activity. Using a functional approach to determine the network of genes affected by La in the cytoplasm by microarray analysis of polysome-bound mRNAs, we found that La binds 34% of the polysome bound mRNAs and regulates the expression of a specific pool of mRNAs under KRas/Akt activation. Therefore, La appears to be an important contributor to Aktmediated translational regulation of these transcripts in murine glial cells.

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Section: Introductionmentioning

confidence: 99%

Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

et al. 2008

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“…Unlike with La, the sequences/secondary structures of the vRNA required for its binding to TEP1 have not yet been determined. Interestingly, in addition to an RNA binding domain, TEP1 also contains a Walker A motif, which in La has been shown to interact with the 5Ј-ppp of pre-tRNAs (27). Because the vRNA is not capped and has a 5Ј-pppG, this motif may be another binding site for interaction with La and/or TEP1.…”

Section: Tep1 Vparp and Vrna Are Not Exclusivelymentioning

confidence: 99%

The La RNA-binding Protein Interacts with the Vault RNA and Is a Vault-associated Protein

Kickhoefer

Poderycki

Chan

et al. 2002

Journal of Biological Chemistry

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Vaults are highly conserved ubiquitous ribonucleoprotein particles with an undefined function. Three protein species (p240/TEP1, p193/VPARP, and p100/MVP) and a small RNA comprise the 13-MDa vault particle. The expression of the unique 100-kDa major vault protein is sufficient to form the basic vault structure. Previously, we have shown that stable association of the vault RNA with the vault particle is dependent on its interaction with the p240/TEP1 protein. To identify other proteins that interact with the vault RNA, we used a UV-cross-linking assay. We find that a portion of the vault RNA is complexed with the La autoantigen in a separate smaller ribonucleoprotein particle. La interacts with the vault RNA (both in vivo and in vitro) presumably through binding to 3 -uridylates. Moreover, we also demonstrate that the La autoantigen is the 50-kDa protein that we have previously reported as a protein that co-purifies with vaults.

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“…The concentration of La protein in the S100 extract of HeLa cells is calculated to be 50 nM (Fan et al, 1998). It would appear that binding of La protein to JEV RNA is physiologically plausible, and using a co-immunoprecipitation experiment, we demonstrated that the JEV genome did indeed interact with endogenous La in JEV-infected HEK293A cells.…”

Section: Discussionmentioning

confidence: 78%

La protein binds the predicted loop structures in the 3′ non-coding region of Japanese encephalitis virus genome: role in virus replication

Vashist

Anantpadma

Sharma

et al. 2009

Journal of General Virology

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Japanese encephalitis virus (JEV) genome is a single-stranded, positive-sense RNA with noncoding regions (NCRs) of 95 and 585 bases at its 59 and 39 ends, respectively. These may bind to viral or host proteins important for viral replication. It has been shown previously that three proteins of 32, 35 and 50 kDa bind the 39 stem-loop (SL) structure of the JEV 39 NCR, and one of these was identified as 36 kDa Mov34 protein. Using electrophoretic mobility-shift and UV cross-linking assays, as well as a yeast three-hybrid system, it was shown here that La protein binds to the 39 SL of JEV. The binding was stable under high-salt conditions (300 mM KCl) and the affinity of the RNA-protein interaction was high; the dissociation constant (K d ) for binding of La protein to the 39 SL was 12 nM, indicating that this RNA-protein interaction is physiologically plausible. Only the N-terminal half of La protein containing RNA recognition motifs 1 and 2 interacted with JEV RNA. An RNA toe-printing assay followed by deletion mutagenesis showed that La protein bound to predicted loop structures in the 39 SL RNA. Furthermore, it was shown that small interfering RNA-mediated downregulation of La protein resulted in repression of JEV replication in cultured cells. INTRODUCTIONJapanese encephalitis virus (JEV) is the single most important causative agent of epidemic viral encephalitis in South-East Asia, leading to around 50 000 clinical cases annually with up to 10 000 deaths. JEV is a mosquito-borne virus belonging to the animal virus family Flaviviridae. The JEV genome consists of a single-stranded, positive-sense RNA of~11 kb, having a type I cap with no polyadenylation at the 39 end. The genomic RNA contains a single open reading frame (ORF) encoding a polyprotein of~3400 aa. The polyprotein is subsequently cleaved by viral and host proteases into three structural (capsid, pre-M and envelope) and seven non-structural (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) proteins. The ORF of the JEV genome is flanked by 59 and 39 non-coding regions (NCRs) of 95 and 585 bases, respectively (Chambers et al., 1990). Although the size and sequence of the NCRs is not well conserved among different flaviviruses, several conserved features and secondary structures have been elucidated. For example, the last 80-90 nt at the extreme 39 end of the 39 NCR have been predicted to form a stable stem-loop (SL) structure in different flaviviruses (Brinton et al., 1986;Shi et al., 1996;Takegami et al., 1986). Whilst the size and shape of the 39 SL structure is highly conserved, sequence conservation is restricted to its loop regions and to 27 nt immediately upstream of the structure. The conservation of this location and the RNA structure in the NCRs of flaviviruses indicates their functional significance.The positive-sense genomic RNA is converted to a replication-intermediate negative-sense RNA during the course of flavivirus replication, as with other positive-sense RNA viruses. The negative-sense RNA acts as template for the synthesis of positive-sense...

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5′ Processing of tRNA Precursors Can Be Modulated by the Human La Antigen Phosphoprotein

Cited by 108 publications

References 46 publications

Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

The La RNA-binding Protein Interacts with the Vault RNA and Is a Vault-associated Protein

La protein binds the predicted loop structures in the 3′ non-coding region of Japanese encephalitis virus genome: role in virus replication

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