Model of the SNB architecture in HeLa cells. (A) The SNB is formed by a combination of two distinct substructures, each of which is built on distinct arcRNAs (red and blue wavy lines). HNRNPL acts as the adaptor of the two substructures, namely, the Sam68 substructure (orange circle) and the DBC1 substructure (blue circle), to form the intact SNB in HeLa, SW-13, and T24 cells. The SNB can be separated into two substructures upon knockdown of HNRNPL (siHNRNPL). The Sam68 substructure disappears and the DBC1 substructure remains under certain conditions, including knockdown of either Sam68 or HNRNPD (siSam68 or siHNRNPD) and cold shock, and in specific cell lines such as HCT116 and NIH3T3. (B) Molecular interactions within SNB. In the Sam68 substructure (orange rectangle on the right), the RRM and PLD of HNRNPD (pink circle), which are essential to form the SNB, likely interact with the putative arcRNA (red wavy line) and Sam68 (orange circle)/HNRNPD, respectively. Sam68 likely interacts with the putative arcRNA through the KH domain (KH). In the DBC1 substructure (blue rectangle on the left), DBC1 interacts with the putative arcRNA (blue wavy line) through the N-terminal S1L domain. HNRNPL acts as the adaptor (green circle) of the two substructures. RRM1 and RRM2 (shown as 1 and 2) of HNRNPL may directly or indirectly interact with the putative arcRNA for the DBC1 substructure. X is a hypothetical protein. RRM3 and RRM4 (shown as 3 and 4) likely interact with the putative arcRNA for the Sam68 substructure. PR acts to facilitate the interaction of HNRNPL with the Sam68 substructure. At least two HNRNPL molecules cooperatively function as the adaptor to combine the two substructures. RNA–protein interactions and protein–protein interactions are represented by black and brown arrows, respectively.