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mRNA degradation controls differentiation state-dependent differences in transcript and splice variant abundance

机译:mRNA降解控制转录和剪接变异体丰度的分化状态依赖性差异

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摘要

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.
机译:表达谱实验通常提供信使RNA(mRNA)水平的静态快照。对mRNA合成和降解动力学的更好的了解将有助于控制基因表达的健全的生物信息学模型的发展。我们使用全基因组外显子阵列研究了增殖和分化的成肌细胞中的mRNA稳定性,并报道了约7000个mRNA的衰减率(半衰期)。我们表明,许多mRNA的稳定性在很大程度上取决于分化状态,并导致这些mRNA丰度的差异。另外,事实证明替代剪接与mRNA降解偶联。尽管可以以可比较的水平产生不同的剪接形式,但是它们的相对丰度部分取决于它们在增殖和分化细胞中的不同稳定性。以前认为3'-非翻译区(3'-UTR)包含大多数RNA稳定和去稳定元素,我们证明了共享相同3'-UTR的转录本同工型也适用。 Itga7中有两个剪接变体,其中带有额外内部外显子的同工型在分化细胞中高度稳定,但在增殖细胞的细胞质中优先降解。总之,稳定性和降解的控制成为mRNA转录本和剪接变体差异表达的重要决定因素。

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