ABSTRACT

LARP1 is an oncogenic RNA-binding protein required for ribosome biogenesis and cancer cell survival. From published in vitro studies, there is disparity over which of two different LARP1 protein isoforms (termed the long LI-LARP1 and short SI-LARP1) is the canonical. Here, after conducting a series of biochemical and cellular assays, we conclude that LI-LARP1 (NM_033551.3 > NP_056130.2) is the dominantly expressed form. We observe that SI-LARP1 (NM_015315.5> NP_056130.2) is epigenetically repressed and that this repression is evolutionarily conserved in all but a small subclade of mammalian species. As with other LARP family members, there are multiple potential LARP1 mRNA isoforms that appear to be censored within the nucleus. The capacity of the cell to modulate splicing and expression of these apparently ‘redundant’ mRNAs hints at contextually specific mechanisms of LARP1 expression.

 抽象的

LARP1 是核糖体生物发生和癌细胞存活所需的致癌 RNA 结合蛋白。从已发表的体外研究来看，两种不同的 LARP1 蛋白亚型（称为长 LI-LARP1 和短 SI-LARP1）中哪一种是典型的存在差异。在这里，经过一系列生化和细胞测定后，我们得出结论，LI-LARP1 (NM_033551.3 > NP_056130.2) 是主要表达形式。我们观察到 SI-LARP1 (NM_015315.5> NP_056130.2) 受到表观遗传抑制，并且这种抑制在除了一小部分哺乳动物物种之外的所有哺乳动物中都是进化保守的。与其他 LARP 家族成员一样，有多种潜在的 LARP1 mRNA 亚型似乎在细胞核内受到审查。细胞调节这些明显“冗余”mRNA 的剪接和表达的能力暗示了 LARP1 表达的上下文特异性机制。