Shock Jennifer L, Fischer Kael F, DeRisi Joseph L
Department of Biochemistry and Biophysics, University of California San Francisco, 1700 4th Street, San Francisco, California 94158-2330, USA.
Genome Biol. 2007;8(7):R134. doi: 10.1186/gb-2007-8-7-r134.
The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiologic role, and plays an important role in determining levels of gene expression.
We used a genome-wide approach to characterize mRNA decay in Plasmodium falciparum. We found that, globally, rates of mRNA decay increase dramatically during the asexual intra-erythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 min, but this was extended to an average of 65 min during the late schizont stage of development. Thus, a major determinant of mRNA decay rate appears to be linked to the stage of intra-erythrocytic development. Furthermore, we found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes.
Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intra-erythrocytic development. This type of genome-wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum.
mRNA 衰变率是所有生物体转录后调控的一个基本要素。此前，对多种生物体的研究发现，每个 mRNA 的特定半衰期与其生理作用精确相关，并在决定基因表达水平方面发挥重要作用。
我们采用全基因组方法来表征恶性疟原虫中的 mRNA 衰变。我们发现，总体而言，在无性红细胞内发育周期中，mRNA 衰变率急剧增加。在周期的环状体阶段，mRNA 的平均半衰期为 9.5 分钟，但在发育的晚期裂殖体阶段，这一半衰期延长至平均 65 分钟。因此，mRNA 衰变率的一个主要决定因素似乎与红细胞内发育阶段有关。此外，我们发现衰变模式存在特定变化，叠加在半衰期逐渐延长的主要趋势之上。这些衰变模式的变化在具有特定细胞功能或过程的基因中经常富集。
阐明疟原虫 mRNA 衰变率，通过补充和扩展先前的 mRNA 丰度研究，为解读该寄生虫的遗传控制机制提供了一个关键要素。我们的结果表明，在红细胞内发育的裂殖体阶段，mRNA 衰变率功能的阶段性逐渐降低是 mRNA 积累的一个主要决定因素。这种全基因组范围内 mRNA 衰变率的变化在迄今为止的任何其他生物体中都未观察到，这表明转录后调控可能是恶性疟原虫基因调控的主要机制。
