Abstract
Passage through mitosis is driven by precisely-timed changes in transcriptional regulation and protein degradation. However, the importance of translational regulation during mitosis remains poorly understood. Here, using ribosome profiling, we find both a global translational repression and identified ~200 mRNAs that undergo specific translational regulation at mitotic entry. In contrast, few changes in mRNA abundance are observed, indicating that regulation of translation is the primary mechanism of modulating protein expression during mitosis. Interestingly, 91% of the mRNAs that undergo gene-specific regulation in mitosis are translationally repressed, rather than activated. One of the most pronounced translationally-repressed genes is Emi1, an inhibitor of the anaphase promoting complex (APC) which is degraded during mitosis. We show that full APC activation requires translational repression of Emi1 in addition to its degradation. These results identify gene-specific translational repression as a means of controlling the mitotic proteome, which may complement post-translational mechanisms for inactivating protein function.
Highlights
IntroductionGenome-wide microarray, RNA sequencing (RNA-seq), and protein-based mass spectrometry studies have revealed changes in the abundance of hundreds of proteins during the cell cycle (Cho et al, 2001; Whitfield et al, 2002; Aviner et al, 2013; Grant et al, 2013; Lane et al, 2013; Stumpf et al, 2013; Ly et al, 2014), many of which are expressed in G2 phase and mitosis (G2/M)
Regulated protein degradation plays a key role in sculpting the proteome during the cell cycle, at the end of mitosis when a large set of proteins is ubiquitinated by the E3 ubiquitin ligase, the Anaphase Promoting Complex (APC), and degraded by the proteasome (Peters, 2006)
This sequence information allows the calculation of the average number of ribosomes per messenger RNA (mRNA), which reports on the translation efficiency (TE) of each mRNA
Summary
Genome-wide microarray, RNA sequencing (RNA-seq), and protein-based mass spectrometry studies have revealed changes in the abundance of hundreds of proteins during the cell cycle (Cho et al, 2001; Whitfield et al, 2002; Aviner et al, 2013; Grant et al, 2013; Lane et al, 2013; Stumpf et al, 2013; Ly et al, 2014), many of which are expressed in G2 phase and mitosis (G2/M). Transcriptional regulation plays an important role in this temporal expression pattern, as many genes show cell cycle-stage specific expression of their mRNA level (Cho et al, 2001; Whitfield et al, 2002). Translational regulation plays a important role during the specialized cell division cycles of meiosis and early embryonic development, since transcription is largely silent at this stage (Mendez and Richter, 2001; Groisman et al, 2002; Tadros and Lipshitz, 2009; Weill et al, 2012). While somatic cells appear to use transcriptional regulation as a major mechanism for modulating protein expression during the cell cycle, translational regulation
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