Heart-specific splice-variant of a human mitochondrial ribosomal protein (mRNA processing; tissue specific splicing)

It has been proposed that splice-variants of proteins involved in mitochond rial RNA processing and translation may be involved in the tissue specifici ty of mitochondrial DNA disease mutations (Fischel-Ghodsian, 1998. Mel. Gen et. Metab. 65, 97-104). To identify and characterize the structural compone nts of mitochondrial RNA processing and translation, the Mammalian Mitochon drial Ribosomal Consortium has been formed. The 338 amino acid (aa) residue s long MRP-LS was identified (O'Brien et al., 1999. J. Biol. Chem. 274, 360 43-36051), and its transcript was screened for tissue specific splice-varia nts. Screening of the EST databases revealed a single putative splice-varia nt, due to the insertion of an exon consisting of 89 nucleotides prior to t he last exon. Screening of multiple cDNA libraries revealed this inserted e xon to be present only in heart tissue, in addition to the predominant MRP- LS transcript. Sequencing of this region confirmed the EST sequence, and sh owed in the splice-variant a termination triplet at the beginning of the la st exon. Thus the inserted exon replaces the coding sequence of the regular last exon, and creates a new 353 aa long protein (MRP-L5V1). Sequence anal ysis and 3D modeling reveal similarity between MRP-LS and threonyl-t-RNA sy nthetases, and a likely RNA binding site within MRP-LS, with the C-terminus in proximity to the RNA binding site, Sequence analysis of MRP-L5V1 also s uggests a likely transmembrane domain at the C-terminus. Thus it is possibl e that the MRP-L5V1 C-terminus could interfere with RNA binding and may hav e gained a transmembrane domain. Further studies will be required to elucid ate the functional significance of MRP-L5V1. (C) 2000 Elsevier Science B.V. All rights reserved.