Figure 3. RNA length contributes to regulation of RBP LLPS and MLO dynamics.

(a) RNA length seemingly inversely correlates with its capacity to buffer phase transitions of RBPs (i.e. FUS). The low binding occupancy of short oligonucleotides and/or tRNA molecules may prevent multiple RBP binding, while longer RNAs (i.e. NEAT1_2 lncRNA, rRNA) may contain many binding sites that enable RNA scaffolding of RBP LLPS. Longer RNA length also may promote RNA:RNA interactions that contribute to LLPS and MLO formation, while shorter RNAs have less capacity to form these multivalent RNA/RBP networks. (b) Examples of different intracellular condensates/MLOs that contain RNAs of different lengths. While short RNA oligonucleotides are capable of effectively buffering RBP phase transitions in the cell (i.e. bait RNA oligonucleotides), longer RNAs tend to promote the formation of MLOs and tune their characteristics. MLOs with longer RNA components may exhibit a less dynamic biophysical state (i.e. myogranules, Titin mRNA) than those containing shorter RNA components (i.e. stress granules, non-translating mRNA) due to an increased propensity for RNA self-interaction and reduced molecular exchange.