eIF4A2 promotes 40S ribosome biogenesis in B cells

Eukaryotic initiation factor 4A (eIF4A) plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex, recruiting the 40S small ribosome subunit, and scanning 5' untranslated region (5' UTR) for the start codon. eIF4A1 and eIF4A2, two isoforms of eIF4A, are highly conserved and exchange freely within the eIF4F complex. The understanding of their biological and molecular function remains incomplete if not fragmentary. In this study, we showed that eIF4A1 and eIF4A2 exhibit different expression patterns during B cell development and activation. Mouse genetic analyses showed that they play critical but different roles during B cell development and humoral immune repnsees. While eIF4A1 controls global protein synthesis, eIF4A2 regulates biogenesis of 18S ribosomal RNA and 40S ribosome subunit. This study demonstrates distinct cellular and molecular functions of eIF4A1 and eIF4A2 and unravels a new role of eIF4A2 in controlling 40S ribosome biogenesis.

真核起始因子4A（Eukaryotic initiation factor 4A，eIF4A）可通过形成结合帽结构的eIF4F复合物、招募40S小核糖体亚基并扫描5'非编码区（5' UTR）以定位起始密码子，在细胞mRNA的翻译起始过程中发挥关键作用。eIF4A1与eIF4A2作为eIF4A的两种同工型，在进化上高度保守，且可在eIF4F复合物中自由互换。目前对二者生物学与分子功能的认知即便不算零散不全，也仍不够全面。本研究发现，eIF4A1与eIF4A2在B细胞发育与活化过程中呈现出截然不同的表达模式。小鼠遗传学分析结果显示，二者在B细胞发育与体液免疫应答过程中发挥着关键但各不相同的作用。其中eIF4A1负责调控全局蛋白质合成，而eIF4A2则参与调控18S核糖体RNA与40S核糖体亚基的生物发生。本研究证实了eIF4A1与eIF4A2具有截然不同的细胞与分子功能，并揭示了eIF4A2在调控40S核糖体生物发生方面的全新作用。