Identification of novel lncRNA PANDAR-protein interaction partners involved in splicing regulation

Interactions of long non-coding RNAs (lncRNA) with proteins play important roles in the regulation of many cellular processes. PANDAR (Promotor of CDKN1A Antisense DNA damage Activated RNA) is a lncRNA that is transcribed in a p53-dependent manner from the CDKN1A promoter and is involved in the regulation of proliferation and senescence. Overexpression of PANDAR has been observed in several tumor species and correlated with a poor prognosis for patient survival rate. Depending on the cellular state, PANDAR is known to interact with proteins such as the nuclear transcription factor Y subunit A (NF-YA) and the scaffold attachment factor A (SAF-A). However, a comprehensive analysis of the PANDAR interactome was missing so far.

Researchers at the Chemical Genomics Centre of the Max-Planck Society applied peptide nucleic acid (PNA)-based pull-downs combined with quantitative mass spectrometry to identify new protein binding partners. They confirmed potential candidates like U2AF65 and PTBP1, known to be involved in RNA processing. Furthermore, they observed that overexpression of PANDAR leads to a reduced level of the short pro-apoptotic BCL-X splice variant (BCL-XS) which is regulated by PTBP1. Simultaneous overexpression of PTBP1 was able to rescue this effect. Overall, their data suggest a role for PANDAR in the regulation of splicing events via its interaction partner PTBP1.

Model of PANDAR involved in splicing regulation

At normal and low PANDAR level, PTBP1 is involved in splicing of the BCL-XS short isoform resulting in its upregulation and pro-apoptotic cellular outcome (left). Upon PANDAR upregulation, PANDAR is bound to PTBP1 and functions as a decoy resulting in a decreased level of BCL-XS splice variant leading to a reduced level of pro-apoptotic response (right). Red ribbon: schematic representation of PANDAR.

Pospiech N, Cibis H, Dietrich L, Müller F, Bange T, Hennig S. (2018) Identification of novel PANDAR protein interaction partners involved in splicing regulation. Sci Rep 8(1):2798. [article]