Altered tRNA processing is linked to a distinct and unusual La protein in Tetrahymena thermophila

Abstract

Nascent pre-tRNAs are transcribed by RNA polymerase III and immediately bound by La proteins on the UUU-3’OH sequence, using a tandem arrangement of the La motif and an adjacent RNA recognition motif-1 (RRM1), resulting in protection from 3’-exonucleases and promotion of pre-tRNA folding. The Tetrahymena thermophila protein Mlp1 has been previously classified as a genuine La protein, despite the predicted absence of the RRM1. We find that Mlp1 functions as a La protein through binding of pre-tRNAs, and affects pre-tRNA processing in Tetrahymena thermophila and when expressed in fission yeast. However, unlike in other examined eukaryotes, depletion of Mlp1 results in 3’-trailer stabilization. The 3’-trailers in Tetrahymena thermophila are uniquely short relative to other examined eukaryotes, and 5’-leaders have evolved to disfavour pre-tRNA leader/trailer pairing. Our data indicate that this variant Mlp1 architecture is linked to an altered, novel mechanism of tRNA processing in Tetrahymena thermophila.

NMR Analysis Suggests Synergy between the RRM2 and the Carboxy-Terminal Segment of Human La Protein in the Recognition and Interaction with HCV IRES

“…In addition, we have determined that the La motif alone is capable of binding precursor tRNAs, which are among the in vivo ligands of the La protein [7]. Interestingly, the recent demonstration of an La protein representative in a Tetrahymena that lacks any recognizable RRM motif confirms previous observations and underlines the necessity of studying the individual domains and modules of the La protein in their biological context [24].…”

Enhanced binding of guanylated poly(A) RNA by the LaM domain of LARP1

“…The prototypical LARP gene underwent multiple duplication events to generate specialized isoforms that are conserved across species. It likely contained both LaM and RRM domains since the pair is present in most present day LARP proteins with a few notable exceptions, such as LARP1 [7, 40].…”

The diverse structural modes of tRNA binding and recognition

“…The discriminator base is one of the major identity elements that, in combination with several other nucleotides in the anticodon and the acceptor helix, ensures the very high specificity of aminoacyl-tRNA synthetases ( 43 , 44 ). During the maturation process, 5ʹ leader sequences are excised by the endonuclease RNase P ( 45 ) prior to the 3ʹ trailer, although this order can be reversed for tRNAs harboring long 3ʹ trailer sequences ( 46 ). In the case of the 3ʹ end, the CCA sequence can be encoded in the tRNA gene ( e.g.…”