LARP1 isoform expression in human cancer cell lines

LARP1 is an oncogenic RNA-binding protein required for ribosome biogenesis and cancer cell survival. From published <i>in vitro</i> 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 &gt; NP_056130.2) is the dominantly expressed form. We observe that SI-LARP1 (NM_015315.5&gt; 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.