Looking for Organization Patterns of Highly Expressed Genes: Purine-Pyrimidine Composition of Precursor mRNAs
We analyzed precursor messenger RNAs (pre-mRNAs) of 12 eukaryotic species. In each species, three groups of highly expressed genes, ribosomal proteins, heat shock proteins, and amino-acyl tRNA synthetases, were compared with a control group (randomly selected genes). The purine-pyrimidine (R-Y) composition of pre-mRNAs of the three targeted gene groups proved to differ significantly from the control. The exons of the three groups tested have higher purine contents and R-tract abundance and lower abundance of Y-tracts compared to the control (R-tract—tract of sequential purines with R n ≥ 5; Y-tract—tract of sequential pyrimidines with Y n ≥ 5). In species widely employing “intron definition” in the splicing process, the Y content of introns of the three targeted groups appeared to be higher compared to the control group. Furthermore, in all examined species, the introns of the targeted genes have a lower abundance of R-tracts compared to the control. We hypothesized that the R-Y composition of the targeted gene groups contributes to high rate and efficiency of both splicing and translation, in addition to the mRNA coding role. This is presumably achieved by (1) reducing the possibility of the formation of secondary structures in the mRNA, (2) using the R-tracts and R-biased sequences as exonic splicing enhancers, (3) lowering the amount of targets for pyrimidine tract binding protein in the exons, and (4) reducing the amount of target sequences for binding of serine/arginine-rich (SR) proteins in the introns, thereby allowing SR proteins to bind to proper (exonic) targets.
KeywordsPurine tracts Pyrimidine tracts Splicing efficiency Highly expressed genes Intron definition Exon definition
We thank Ed Trifonov, Zakharia Frenkel, Axel Meyer, and anonymous reviewers for their helpful comments and suggestions. This work was supported by the Israeli Ministry of Absorption and by the Ancell-Teicher Research Foundation for Molecular Genetics and Evolution. A.P. was supported by a scholarship in bioinformatics from the Eshkol Foundation of the Israeli Ministry of Science and Technology.
- Bec G, Kerjan P, Waller JP (1994) Reconstitution in vitro of the valyl-tRNA synthetase-elongation factor (EF) 1 beta gamma delta complex. Essential roles of the NH2-terminal extension of valyl-tRNA synthetase and of the EF-1 delta subunit in complex formation. J Biol Chem 269:2086–2092PubMedGoogle Scholar
- Hsiao LL, Dangond F, Yoshida T, Hong R, Jensen RV, Misra J, Dillon W, Lee KF, Clark KE, Haverty P, Weng Z, Mutter GL, Frosch MP, Macdonald ME, Milford EL, Crum CP, Bueno R, Pratt RE, Mahadevappa M, Warrington JA, Stephanopoulos G, Stephanopoulos G, Gullans SR (2001) A compendium of gene expression in normal human tissues. Physiol Genomics 7:97–104PubMedGoogle Scholar
- Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, Xing G, Dong C, Zhai Y, Wan J, Ouyang S, Li L, Zhang S, Zhou K, Zhang Y, Wu C, He F (2001) Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs. Genome Res 11:1392–1403PubMedCrossRefGoogle Scholar