title: mRNA degradation controls differentiation state-dependent differences in transcript and splice variant abundance.
abstract: Expression profiling experiments usually provide a static snapshot of messenger RNA (mRNA) levels. Improved understanding of the dynamics of mRNA synthesis and degradation will aid the development of sound bioinformatic models for control of gene expression. We studied mRNA stability in proliferating and differentiated myogenic cells using whole-genome exon arrays and reported the decay rates (half life) for ∼7000 mRNAs. We showed that the stability of many mRNAs strongly depends on the differentiation status and contributes to differences in abundance of these mRNAs. In addition, alternative splicing turns out to be coupled to mRNA degradation. Although different splice forms may be produced at comparable levels, their relative abundance is partly determined by their different stabilities in proliferating and differentiated cells. Where the 3'-untranslated region (3'-UTR) was previously thought to contain most RNA stabilizing and destabilizing elements, we showed that this also holds for transcript isoforms sharing the same 3'-UTR. There are two splice variants in Itga7, of which the isoform with an extra internal exon is highly stable in differentiated cells but preferentially degraded in the cytoplasm of proliferating cells. In conclusion, control of stability and degradation emerge as important determinants for differential expression of mRNA transcripts and splice variants.
authors.affiliation: Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. p.a.c.hoen@lumc.nl
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.forename: Michael
authors.initials: M
authors.lastname: Hirsch
authors.forename: Emile J
authors.initials: EJ
authors.lastname: de Meijer
authors.forename: Renée X
authors.initials: RX
authors.lastname: de Menezes
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D006207:Half-Life; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D009124:Muscle Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C085725:integrin alpha7