Decay Rates of Human mRNAs: Correlation With Functional Characteristics and Sequence Attributes

Genome Research - Tập 13 Số 8 - Trang 1863-1872 - 2003
Edward Yang1, Erik van Nimwegen2, Mihaela Zavolan3, Nikolaus Rajewsky4, Mark Schroeder3, Marcelo O. Magnasco5, James Darnell1
1Laboratory of Molecular Cell Biology
2Center for the Study of Physics and Biology, The Rockefeller University, New York, New York 10021-6399, USA;
3Laboratory of Computational Genomics,
4Department of Biology and Courant Institute of Mathematical Sciences, New York University, New York, New York 10012, USA
5Laboratory of Mathematical Physics, and

Tóm tắt

Although mRNA decay rates are a key determinant of the steady-state concentration for any given mRNA species, relatively little is known, on a population level, about what factors influence turnover rates and how these rates are integrated into cellular decisions. We decided to measure mRNA decay rates in two human cell lines with high-density oligonucleotide arrays that enable the measurement of decay rates simultaneously for thousands of mRNA species. Using existing annotation and the Gene Ontology hierarchy of biological processes, we assign mRNAs to functional classes at various levels of resolution and compare the decay rate statistics between these classes. The results show statistically significant organizational principles in the variation of decay rates among functional classes. In particular, transcription factor mRNAs have increased average decay rates compared with other transcripts and are enriched in “fast-decaying” mRNAs with half-lives <2 h. In contrast, we find that mRNAs for biosynthetic proteins have decreased average decay rates and are deficient in fast-decaying mRNAs. Our analysis of data from a previously published study of Saccharomyces cerevisiae mRNA decay shows the same functional organization of decay rates, implying that it is a general organizational scheme for eukaryotes. Additionally, we investigated the dependence of decay rates on sequence composition, that is, the presence or absence of short mRNA motifs in various regions of the mRNA transcript. Our analysis recovers the positive correlation of mRNA decay with known AU-rich mRNA motifs, but we also uncover further short mRNA motifs that show statistically significant correlation with decay. However, we also note that none of these motifs are strong predictors of mRNA decay rate, indicating that the regulation of mRNA decay is more complex and may involve the cooperative binding of several RNA-binding proteins at different sites.

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Tài liệu tham khảo

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Genome Research

Tập 13 Số 8

1863-1872

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