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Mol Cell Biol, June 1998, p. 3201-3211, Vol. 18, No. 6
Laboratory of Molecular Growth Regulation,
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland
20892-2753,1 and
Cellular and Molecular
Biology Program2 and
Department of
Biological Chemistry,3 University of Michigan,
Ann Arbor, Michigan 48109-0606
Received 24 November 1997/Returned for modification 18 January
1998/Accepted 6 March 1998
Eukaryotic precursor (pre)-tRNAs are processed at both ends prior
to maturation. Pre-tRNAs and other nascent transcripts synthesized by
RNA polymerase III are bound at their 3' ends at the sequence motif
UUUOH [3' oligo(U)] by the La antigen, a conserved
phosphoprotein whose role in RNA processing has been associated
previously with 3'-end maturation only. We show that in addition to its
role in tRNA 3'-end maturation, human La protein can also modulate 5' processing of pre-tRNAs. Both the La antigen's N-terminal RNA-binding domain and its C-terminal basic region are required for attenuation of
pre-tRNA 5' processing. RNA binding and nuclease protection assays with
a variety of pre-tRNA substrates and mutant La proteins indicate that
5' protection is a highly selective activity of La. This activity is
dependent on 3' oligo(U) in the pre-tRNA for interaction with the
N-terminal RNA binding domain of La and interaction of the C-terminal
basic region of La with the 5' triphosphate end of nascent pre-tRNA.
Phosphorylation of La is known to occur on serine 366, adjacent to the
C-terminal basic region. We show that this modification interferes with
the La antigen's ability to protect pre-tRNAiMet from
5' processing either by HeLa extract or purified RNase P but that it
does not affect interaction with the 3' end of pre-tRNA. These findings
provide the first evidence to indicate that tRNA 5'-end maturation may
be regulated in eukaryotes. Implications of triphosphate recognition is
discussed as is a role for La phosphoprotein in controlling
transcriptional and posttranscriptional events in the biogenesis of
polymerase III transcripts.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
5' Processing of tRNA Precursors Can Be
Modulated by the Human La Antigen Phosphoprotein
*
Corresponding author. Mailing address: Building 6, Room
416, LMGR, NICHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892-2753. Phone: (301) 402-3567. Fax: (301) 480-6863. E-mail:
maraia{at}ncbi.nlm.nih.gov.
R.J.M. dedicates this research paper to the memory of Christopher
P. Cully.
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