Published online 18 March 2004
Nucleic Acids Research, 2004, Vol. 32, No. 5 1774-1782
© 2004, the authors
Nucleic Acids Research, Vol. 32 No. 5 © Oxford University Press; all rights reserved
Comparative analysis of orthologous eukaryotic mRNAs: potential hidden functional signals
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
*To whom correspondence should be addressed. Tel: +1 301 496 2475; Fax: +1 301 480 9241; Email: lipman{at}ncbi.nlm.nih.gov
Received December 31, 2003; Revised and Accepted February 5, 2004
Sequencing of multiple, nearly complete eukaryotic genomes creates opportunities for detecting previously unnoticed, subtle functional signals in non-coding regions. A genome-wide comparative analysis of orthologous sets of mammalian and yeast mRNAs revealed distinct patterns of evolutionary conservation at the boundaries of the untranslated regions (UTRs) and the coding region (CDS). Elevated sequence conservation was detected in 
30 nt regions around the start codon. There seems to be a complementary relationship between sequence conservation in the 30 nt regions of the 5'-UTR immediately upstream of the start codon and that in the synonymous positions of the 5'-terminal 30 nt of the CDS: in mammalian mRNAs, the 5'-UTR shows a greater conservation than the CDS, whereas the opposite trend holds for yeast mRNAs. Unexpectedly, a 30 nt region downstream of the stop codon shows a substantially lower level of sequence conservation than the downstream portions of the 3'-UTRs. However, the sequence in this poorly conserved 30 nt portion of the 3'-UTR is non-random in that it has a higher GC content than the rest of the UTR. It is hypothesized that the elevated sequence conservation in the region immediately upstream of the start codon is related to the requirement for initiation factor binding during pre-initiation ribosomal scanning. In contrast, the poorly conserved region downstream of the stop codon could be involved in the post- termination scanning and dissociation of the ribosomes from the mRNA, which requires only the mRNA–ribosome interaction. Additionally, it was found that the choice of the stop codon in mammals, but not in yeasts, and the context in the immediate vicinity of the stop codons in both mammals and yeasts are subject to strong selection. Thus, genome-wide analysis of orthologous gene sets allows detection of previously unrecognized patterns of sequence conservation, which are likely to reflect hidden functional signals, such as ribosomal filters that could regulate translation by modulating the interaction between the mRNA and ribosomes.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Hazle and L. Bonen Comparative Analysis of Sequences Preceding Protein-Coding Mitochondrial Genes in Flowering Plants Mol. Biol. Evol., May 1, 2007; 24(5): 1101 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Hong, D. G. Scofield, and M. Lynch Intron Size, Abundance, and Distribution within Untranslated Regions of Genes Mol. Biol. Evol., December 1, 2006; 23(12): 2392 - 2404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Shabalina, A. Y. Ogurtsov, and N. A. Spiridonov A periodic pattern of mRNA secondary structure created by the genetic code. Nucleic Acids Res., January 1, 2006; 34(8): 2428 - 2437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Churbanov, I. B. Rogozin, V. N. Babenko, H. Ali, and E. V. Koonin Evolutionary conservation suggests a regulatory function of AUG triplets in 5'-UTRs of eukaryotic genes Nucleic Acids Res., September 26, 2005; 33(17): 5512 - 5520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Kochetov AUG codons at the beginning of protein coding sequences are frequent in eukaryotic mRNAs with a suboptimal start codon context Bioinformatics, April 1, 2005; 21(7): 837 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Fritz, D. Liu, J. Xu, S. Jiang, and M. B. Rogers Conservation of Bmp2 Post-transcriptional Regulatory Mechanisms J. Biol. Chem., November 19, 2004; 279(47): 48950 - 48958. [Abstract] [Full Text] [PDF]
|
|