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Review
. 2001 Jan;21(2):367-79.
doi: 10.1128/MCB.21.2.367-379.2001.

Recognition of nascent RNA by the human La antigen: conserved and divergent features of structure and function

R J Maraia  1 , R V Intine
Affiliations
Review

Recognition of nascent RNA by the human La antigen: conserved and divergent features of structure and function

R J Maraia et al. Mol Cell Biol. 2001 Jan.
No abstract available

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Figures

FIG. 1
FIG. 1
Modeling of the proposed RRM-1 in the highly conserved, N-terminal region of La protein. Alignment of 13 La sequences (beginning with H. sapiens La and ending with A. thaliana La) available in the protein database was performed by ClustalW. Only the sequences that appeared to be full-length La proteins were included in the alignment, and of these, several have been characterized biochemically as authentic RNA-binding proteins (see text). The sequences aligned here correspond to residues 20 to 92 of hLa (numbered above only for H. sapiens La). Invariant residues are reverse shaded in black columns; conserved residues are in gray columns. The top line reflects the output of the Quadratic logistic secondary structure prediction with homologous sequences (QL w/hom) program (39); H, α helix; E, extended β strand; C, non-α-helix, non-β-strand. Below this is indicated the RRM topology β1-loop 1-α1-loop 2-β-loop 3-β3-loop 4-α2-loop 5-β4 that is used for aligning the RRM core hydrophobic residues according to the work of Birney et al. (14). Below the alignment set is the La consensus (“La cons”) line, in which invariant residues are shown in uppercase; Φ = Y or F; other conserved residues are represented according to the designations of Birney; U = uncharged (L, I, V, A, G, F, W, Y, C, or M); Z = U + S, T. Candidate residues that may be involved in uridylate recognition are underlined (see text). The positions of the putative RNP-2 (in β1) and RNP-1 (in β3) motifs of RRM-1 (La RNPs-2&1) are indicated by horizontal lines. The “La RRM CORE” is shown for comparison to the conserved “RRM CORE” structure according to reference . The “CORE con” line shows the RRM core with spacing according to reference . The sequences and accession numbers are as follows: H. sapiens (Hs), P05455; B. taurus (Bt), P10881; R. norvegicus (Rn), P38656; M. musculus (Mm), P32067; X. laevis La-B (Xb), P28049; X. laevis La-A (Xa), P28048; A. albopictus (Aa), Q26457; Caenorhabditis elegans (Ce), T30953; D. melanogaster (Dm), P40796; T. brucei (Tb), AAF34598.1; S. pombe (Sp), AAB82145.1; S. cerevisiae (Sc), P33399; A. thaliana (At), AAF09063.
FIG. 2
FIG. 2
Schematic representation of hLa and its apparent mode of bipartite interaction with a model precursor tRNA and comparison to three other La proteins. Cartoon alignment of the La proteins of human (hLa), D. melanogaster (dLa), S. pombe (Sla1p), and S. cerevisiae (Lhp1p), representatives of four phylogenetic branches according to the work of Rosenblum et al. (117). Note that these represent four polypeptides that have been characterized as UUU-OH-binding proteins that associate with nascent Pol III transcripts in vivo (83, 136, 139, 153). Their lengths, in amino acids, are indicated at the right. RRM-1, -2, and -3 domains are shaded and labeled for hLa only. Invariant residues in the 13 sequences are shown as vertical lines; note that these are limited to RRM-1. The invariant residues (numbered according to hLa) are Q20, E22, Y24, F25, N29, D33, F35, L36, G45, V47, F55, R57, A71, and R91. The linker between RRM-1 and RRM-2 is hatched. A putative WAM and PBS and serine 366 (encircled S) are shown (see text). Positions of the NLS are indicated in boldface according to reference . A consensus NLS in hLa, as noted previously (131), is shown in lightface. A schematized pre-tRNA has been imposed above the hLa cartoon to illustrate its proposed orientation according to a model based on prior work (41, 67) as described in the text.
FIG. 3
FIG. 3
A model of phosphorylation-regulated, bipartite precursor tRNA binding by the hLa protein. The model shown here depicts bipartite interactions with a nascent pre-tRNA according to previous data (41, 67) and the model in Fig. 2. The tandem RRM-1 and -2 of the NTD mediate high-affinity binding to UUU-OH-containing RNAs. The CTD of hLa contains a basic region and an acidic region, shown as +++ and −−, respectively; residues 328 to 344 conform to a WAM, and residues 348 to 368 represent a putative PBS (see Fig. 2 and text). Together, the WAM and PBS can recognize the 5′-pppG/A motif that comprises the 5′ ends of nascent Pol III transcripts (41, 67). Serine 366, which resides in a region that demarcates a transition from basic to acidic residues, is shown as S in unphosphorylated La and as P in the phosphoserine form.
See this image and copyright information in PMC

References

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