Genome Analysis Reveals Interplay between 5′UTR Introns and Nuclear mRNA Export for Secretory and Mitochondrial Genes

In higher eukaryotes, messenger RNAs (mRNAs) are exported from the nucleus to the cytoplasm via factors deposited near the 5′ end of the transcript during splicing. The signal sequence coding region (SSCR) can support an alternative mRNA export (ALREX) pathway that does not require splicing. However, most SSCR–containing genes also have introns, so the interplay between these export mechanisms remains unclear. Here we support a model in which the furthest upstream element in a given transcript, be it an intron or an ALREX–promoting SSCR, dictates the mRNA export pathway used. We also experimentally demonstrate that nuclear-encoded mitochondrial genes can use the ALREX pathway. Thus, ALREX can also be supported by nucleotide signals within mitochondrial-targeting sequence coding regions (MSCRs). Finally, we identified and experimentally verified novel motifs associated with the ALREX pathway that are shared by both SSCRs and MSCRs. Our results show strong correlation between 5′ untranslated region (5′UTR) intron presence/absence and sequence features at the beginning of the coding region. They also suggest that genes encoding secretory and mitochondrial proteins share a common regulatory mechanism at the level of mRNA export.在高等真核生物中，信使RNA（mRNA）经由剪接过程中沉积于转录本5'端附近的转运因子，从细胞核被转运至细胞质。信号序列编码区（SSCR）可介导一条无需剪接的替代性mRNA转运（ALREX）通路。然而，大多数携带SSCR的基因同时含有内含子，因此这两种转运机制之间的相互作用仍有待阐明。本研究提出的模型指出，给定转录本中最上游的元件——无论是内含子还是促进ALREX的SSCR——将决定该转录本所采用的mRNA转运通路。本研究还通过实验证实，核编码线粒体基因亦可采用ALREX通路。由此可见，线粒体靶向序列编码区（MSCR）内的核苷酸信号同样可介导ALREX通路。本研究最终鉴定并通过实验验证了一类与ALREX通路相关的新型基序，这类基序同时存在于SSCR和MSCR中。研究结果显示，5'非翻译区（5'UTR）是否含有内含子，与编码区起始区域的序列特征存在显著相关性。该结果还表明，编码分泌蛋白与线粒体蛋白的基因，在mRNA转运层面共享一套保守的调控机制。