Have tRNA, will travel

Phizicky, Eric M.

doi:10.1073/pnas.0504843102

Cited by 15 publications

(15 citation statements)

References 37 publications

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“…Rather, functional unmasking or overriding of the nuclear export activity of La by the NRE appears to be detrimental to tRNA maturation. Thus, the data in this report do not support a positive role for La in tRNA nucleocytoplasmic transport, as speculated previously (29). The fact that we could identify mutations of conserved residues that block export without impairing tRNA maturation (e.g., hLa E132/D133 and Sla1p E177/E178) suggests that these residues were conserved to function in an important process other than tRNA maturation that involves nuclear export.…”

Section: Discussionsupporting

confidence: 49%

“…Removal of the 3Ј trailer is believed to occur in the nucleus, as do some modifications, CCA addition, and aminoacylation (9,24,42). The discovery that tRNA splicing occurs in the cytoplasm in yeast (44) is consistent with splicing occurring after 5Ј end processing (9,29). An equally surprising discovery which revealed further complexity was that tRNAs can move in a "retrograde" manner, from the cytoplasm to the nucleus (29,33,36).…”

mentioning

confidence: 62%

“…These findings coupled with discoveries of cytoplasmic splicing and retrograde transport led to a suggestion that La may be involved in tRNA transport (29).…”

mentioning

confidence: 99%

“…The discovery that tRNA splicing occurs in the cytoplasm in yeast (44) is consistent with splicing occurring after 5Ј end processing (9, 29). An equally surprising discovery which revealed further complexity was that tRNAs can move in a "retrograde" manner, from the cytoplasm to the nucleus (29,33,36). Retrograde tRNA transport may also occur in mammals (45).…”

mentioning

confidence: 99%

“…Nascent pre-tRNAs require 5Ј and 3Ј end processing, numerous modifications, CCA addition, aminoacylation, nuclear export, and splicing, if necessary, prior to the appearance of a mature functional tRNA in the cytoplasm (9). Recent findings have revealed that the tRNA production pathway is highly complex in biochemistry, spatial organization, and sequential order (9,29). In what order are the 5Ј leader, intron, and 3Ј trailer normally removed from a pretRNA, and in which cellular compartments do these reactions occur?…”

mentioning

confidence: 99%

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Conservation of a Masked Nuclear Export Activity of La Proteins and Its Effects on tRNA Maturation

Bayfield

Kaiser

Intine

et al. 2007

Molecular and Cellular Biology

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La is an RNA-processing-associated phosphoprotein so highly conserved that the human La protein (hLa) can replace the tRNA-processing function of the fission yeast La protein (Sla1p) in vivo. La proteins contain multiple trafficking elements that support interactions with RNAs in different subcellular locations. Prior data indicate that deletion of a nuclear retention element (NRE) causes nuclear export of La and dysfunctional processing of associated pre-tRNAs that are spliced but 5 and 3 unprocessed, with an accompanying decrease in tRNA-mediated suppression, in fission yeast. To further pursue these observations, we first identified conserved residues in the NREs of hLa and Sla1p that when substituted mimic the NRE deletion phenotype. NRE-defective La proteins then deleted of other motifs indicated that RNA recognition motif 1 (RRM1) is required for nuclear export. Mutations of conserved RRM1 residues restored nuclear accumulation of NREdefective La proteins. Some RRM1 mutations restored nuclear accumulation, prevented disordered pre-tRNA processing, and restored suppression, indicating that the tRNA-related activity of RRM1 and its nuclear export activity could be functionally separated. When mapped onto an hLa structure, the export-sensitive residues comprised surfaces distinct from the RNA-binding surface of RRM1. The data indicate that the NRE has been conserved to mask or functionally override an equally conserved nuclear export activity of RRM1. The data suggest that conserved elements mediate nuclear retention, nuclear export, and RNA-binding activities of the multifunctional La protein and that their interrelationship contributes to the ability of La to engage its different classes of RNA ligands in different cellular locations.La is an abundant protein whose capacity to bind a variety of noncoding RNAs and mRNAs lends itself to numerous activities (26). La proteins from yeast to human have been implicated in the production of tRNAs, rRNAs, ribosomal proteins, and other components of the translational machinery (13,16,19,20). In human cells, most La is phosphorylated on serine-366 by protein kinase CK2, resides in the nucleoplasm, and is associated with nascent pre-tRNAs (17, 32). Nonphosphorylated La is most concentrated in the nucleolus (15, 16) and was independently found at tRNA and other RNA polymerase III-transcribed genes (4), but it also resides in the cytoplasm associated with 5ЈTOP mRNAs that encode ribosomal proteins and translation factors (16). Trafficking signals in human La include a nuclear localization signal (NLS), a nuclear retention element (NRE) first identified by microinjection of Xenopus oocytes and later confirmed in fission yeast (14,35), and a nucleolar localization signal (10, 15). Although trafficking may be important for its different activities (19), knowledge of the functional significance of alterations in La trafficking in specific RNA pathways is limited.Sequence-specific binding to 3Ј UUU-OH, the termination motif found on nascent pre-tRNAs and other transcripts syn...

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Section: Discussionsupporting

confidence: 49%

mentioning

confidence: 62%

“…These findings coupled with discoveries of cytoplasmic splicing and retrograde transport led to a suggestion that La may be involved in tRNA transport (29).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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