The relationship between the evolution of microRNA targets and the length of their UTRs

BackgroundMicroRNAs (miRNAs) are endogenous small RNA molecules that modulate the gene expression at the post-transcription levels in many eukaryotic cells. Their widespread and important role in animals is gauged by estimates that ~25% of all genes are miRNA targets.ResultsWe perform a systematic investigation of the relationship between miRNA regulation and their targets' evolution in two mammals: human and mouse. We find genes with longer 3' UTRs are regulated by more distinct types of miRNAs. These genes correspondingly tend to have slower evolutionary rates at the protein level. Housekeeping genes are another class of genes that evolve slowly. However, they have a distinctly different type of regulation, with shorter 3'UTRs to avoid miRNA targeting.ConclusionOur analysis suggests a two-way evolutionary mechanism for miRNA targets on the basis of their cellular roles and the length of their 3' UTRs. Functionally critical genes that are spatially or temporally expressed are stringently regulated by miRNAs. While housekeeping genes, however conserved, are selected to have shorter 3'UTRs to avoid miRNA regulation.

[1]  E. Levanon,et al.  Human housekeeping genes are compact. , 2003, Trends in genetics : TIG.

[2]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[3]  Mihaela Zavolan,et al.  Inference of miRNA targets using evolutionary conservation and pathway analysis , 2007, BMC Bioinformatics.

[4]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[5]  E. Lai Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation , 2002, Nature Genetics.

[6]  A. E. Hirsh,et al.  Protein dispensability and rate of evolution , 2001, Nature.

[7]  G. Hannon,et al.  Control of translation and mRNA degradation by miRNAs and siRNAs. , 2006, Genes & development.

[8]  David I. K. Martin,et al.  MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Sudhir Kumar,et al.  Gene Expression Intensity Shapes Evolutionary Rates of the Proteins Encoded by the Vertebrate Genome , 2004, Genetics.

[10]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[12]  Anton J. Enright,et al.  MicroRNA targets in Drosophila , 2003, Genome Biology.

[13]  S. Yi,et al.  Correlated asymmetry of sequence and functional divergence between duplicate proteins of Saccharomyces cerevisiae. , 2006, Molecular biology and evolution.

[14]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[15]  Anton J. Enright,et al.  Human MicroRNA Targets , 2004, PLoS biology.

[16]  Donglin Liu,et al.  BIOINFORMATICS APPLICATIONS NOTE Databases and ontologies PACdb: PolyA Cleavage Site and 3 ′-UTR Database , 2022 .

[17]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information , 2021, Nucleic Acids Res..

[18]  Uwe Ohler,et al.  Spatial preferences of microRNA targets in 3' untranslated regions , 2007, BMC Genomics.

[19]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[20]  R. Plasterk,et al.  The diverse functions of microRNAs in animal development and disease. , 2006, Developmental cell.

[21]  R. Russell,et al.  Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution , 2005, Cell.

[22]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[23]  V. Ambros,et al.  Role of MicroRNAs in Plant and Animal Development , 2003, Science.

[24]  P. Sharp,et al.  Proliferating Cells Express mRNAs with Shortened 3' Untranslated Regions and Fewer MicroRNA Target Sites , 2008, Science.

[25]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[26]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[27]  Hong Duan,et al.  The regulatory activity of microRNA* species has substantial influence on microRNA and 3′ UTR evolution , 2008, Nature Structural &Molecular Biology.

[28]  N. Rajewsky,et al.  Natural selection on human microRNA binding sites inferred from SNP data , 2006, Nature Genetics.

[29]  V. Ambros The functions of animal microRNAs , 2004, Nature.

[30]  C. Burge,et al.  The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution , 2005, Science.

[31]  W. Murphy,et al.  Resolution of the Early Placental Mammal Radiation Using Bayesian Phylogenetics , 2001, Science.