Novel tRNA-like transcripts from the NEAT1-MALAT1 genomic region critically influence human innate immunity and macrophage functions

The evolutionary conserved NEAT1-MALAT1 gene cluster generates large noncoding transcripts remaining nuclear, while tRNA-like transcripts (mascRNA, menRNA) enzymatically generated from these precursors translocate to the cytosol. Beyond prior work documenting immune function of the NEAT1-MALAT1 cluster, the current study identifies menRNA and mascRNA as novel elements of innate immunity impacting upon cytokine regulation, immune cell-endothelium interactions, angiogenesis, and monocyte-macrophage differentiation and functions. These molecules are prototypes of a new class of RNAs distinct from other small transcripts (miRNAs, siRNAs) by biosynthetic pathway and intracellular kinetics. From an evolutionary perspective, the NEAT1-MALAT1 genomic region appears as archetype of a functionally highly integrated RNA processing system.