Identification of novel post-transcriptional features in olfactory receptor family mRNAs.
Identification of novel post-transcriptional features in olfactory receptor family mRNAs.
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DOI：
10.1093/nar/gkv324
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发表时间：
2015-10-30
影响因子：
14.9
通讯作者：
Wilkinson MF
中科院分区：
文献类型：
--
作者：
Shum EY;Espinoza JL;Ramaiah M;Wilkinson MF
嗅觉受体（Olfr）基因是小鼠中最大的基因家族。尽管它们在嗅觉中的重要性，但大多数Olfr mRNA是如何调节的仍然未被探索。使用RNA-seq分析结合分析已有的数据库，我们发现Olfr mRNA具有几个非典型特征，表明转录后调控影响其表达。首先，Olfr mRNA作为一个组，与对照mRNA相比具有显著更高的平均AU含量和更低的预测二级结构。第二，Olfr mRNA在其3′UTR中具有更高密度的富含AU的元件（战神），在其5个UTR中具有更高密度的上游开放阅读框（uORF）。第三，Olfr mRNA具有较短的3′ UTR区域和较少的预测的miRNA结合位点。所有这些新特性与更高的Olfr表达相关。我们还确定了显着的差异，转录后功能的mRNA从两个主要类别的Olfr基因，一个发现与它们的独立的进化起源一致。总之，我们的研究结果表明，Olfr基因家族在神经细胞中遇到了不寻常的选择力，这些选择力驱使它们获得独特的转录后调控功能。为了支持这种可能性，我们发现，虽然Olfr mRNA是通过依赖于去腺苷化的机制降解的，但它们在神经谱系细胞中在很大程度上受到保护，不受这种衰变的影响。
Olfactory receptor (Olfr) genes comprise the largest gene family in mice. Despite their importance in olfaction, how most Olfr mRNAs are regulated remains unexplored. Using RNA-seq analysis coupled with analysis of pre-existing databases, we found that Olfr mRNAs have several atypical features suggesting that post-transcriptional regulation impacts their expression. First, Olfr mRNAs, as a group, have dramatically higher average AU-content and lower predicted secondary structure than do control mRNAs. Second, Olfr mRNAs have a higher density of AU-rich elements (AREs) in their 3′UTR and upstream open reading frames (uORFs) in their 5 UTR than do control mRNAs. Third, Olfr mRNAs have shorter 3′ UTR regions and with fewer predicted miRNA-binding sites. All of these novel properties correlated with higher Olfr expression. We also identified striking differences in the post-transcriptional features of the mRNAs from the two major classes of Olfr genes, a finding consistent with their independent evolutionary origin. Together, our results suggest that the Olfr gene family has encountered unusual selective forces in neural cells that have driven them to acquire unique post-transcriptional regulatory features. In support of this possibility, we found that while Olfr mRNAs are degraded by a deadenylation-dependent mechanism, they are largely protected from this decay in neural lineage cells.