Not all TOP RNAs are created equal: 3'UTR length and TSS selection predict the translational regulation of LARP1-bound mRNAs in CD4+ T cells

Translationally repressed ribosomal protein mRNA, known as TOP RNAs, play a crucial role in supporting protein synthesis, cell growth, and proliferation in naive T cells. These RNAs are regulated by an RNA binding protein called LARP1, which stabilizes the transcript and represses translation. In this study, researchers generated cross-linking immunoprecipitation (CLIP) datasets to investigate LARP1 function in T cell activation, specifically focusing on naive and activated CD4+ T cells.

The analysis identified novel TOP RNAs with varying levels of regulation. RP mRNAs, a typical member of this class, exhibited high stability and translational repression in naive T cells, which increased MTORC1-dependent translation following T cell activation. However, other TOP RNAs demonstrated different patterns of regulation.

Specifically, TOP RNAs with longer 3' untranslated regions (3 UTRs) displayed a reduced dependency on LARP1 for stability and MTORC1 for translation. Additionally, the position of the transcription start site (TSS) influenced TOP RNA regulation by creating a mixture of transcript isoforms with varying TOP motif lengths. Longer terminal oligo pyrimidine stretches were linked to a greater dependency on MTORC1 for translation.

These findings suggest that the differential regulation of TOP RNAs enables fine-tuned translational responses to MTORC1 signaling. This indicates potential roles for LARP1 beyond translation regulation and stability, highlighting the complexity of TOP RNA dynamics in T cell activation.