MALTAT1 is the lncRNA which was found to regulate the alternative splicing of pre-mRNAs (Prasanth KV et al., 2010). This lncRNA interacts with the SR proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of MALAT1 or overexpression of an SR protein changes the alternative splicing of a similar set of endogenous pre-mRNAs. Furthermore, MALAT1 regulates cellular levels of phosphorylated forms of SR proteins.

The group demonstrated that MALAT1 localizes to nuclear speckles and interacts with several pre-mRNA splicing factors also the depletion of the same results in an increase in the dephosphorylated pool of SR proteins that display a more homogeneous nuclear distribution. Since the SRSF2 mAb primarily recognizes phosphorylated SR proteins, it likely detects a steady-state pool of residual phosphorylated SR proteins present in MALAT1- depleted speckles (can be seen in figure below). Hyper-Phosphorelated SR domains influence the binding of SR proteins to pre-mRNA and regulate splice site selection by dictating protein-protein and protein-RNA interactions within the spliceosome.

Screenshot - 06172013 - 02:31:46 PM

Advertisements