A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells.

Yuping Mei,Li Mao,Alexander D Mackerell,Priti Kumari,Tyler Gable,Martin J Edelman,Amol Carl Shetty,David J Weber,Austin J Yang,Mark Z Ma,David Clark,Yuyan Wang

doi:10.1038/ncomms8316

Abstract

PIWI-interacting RNAs (piRNAs) are thought to silence transposon and gene expression during development. However, the roles of piRNAs in somatic tissues are largely unknown. Here we report the identification of 555 piRNAs in human lung bronchial epithelial (HBE) and non-small cell lung cancer (NSCLC) cell lines, including 295 that do not exist in databases termed as piRNA-like sncRNAs or piRNA-Ls. Distinctive piRNA/piRNA-L expression patterns are observed between HBE and NSCLC cells. piRNA-like-163 (piR-L-163), the top downregulated piRNA-L in NSCLC cells, binds directly to phosphorylated ERM proteins (p-ERM), which is dependent on the central part of UUNNUUUNNUU motif in piR-L-163 and the RRRKPDT element in ERM. The piR-L-163/p-ERM interaction is critical for p-ERM's binding capability to filamentous actin (F-actin) and ERM-binding phosphoprotein 50 (EBP50). Thus, piRNA/piRNA-L may play a regulatory role through direct interaction with proteins in physiological and pathophysiological conditions.

Highlights

PIWI-interacting RNAs are thought to silence transposon and gene expression during development
RNA sequencing was performed and resulted in B4.5 million reads with 499% of the reads between 26 and 32 bases (Supplementary Fig. 1a and Supplementary Table 1), and B50% of the reads mapped to Z2 loci in the human genome sequences (Supplementary Fig. 1b), indicating that the PIWI-interacting RNAs (piRNAs) reads captured a nontrivial portion of piRNA diversity[33]
In this study, we systematically profiled the expression of piRNAs and piRNA-Ls in adult human airway cells including both immortalized normal HBE (NHBE) and lung cancer cells

Summary

Introduction

PIWI-interacting RNAs (piRNAs) are thought to silence transposon and gene expression during development. The ERM proteins (ezrin, radixin and moesin) belong to a family of proteins located at cell cortex[11,12,13,14] They are critical in connecting transmembrane proteins, such as EBP50 (ERM-binding phosphoprotein 50), and the cytoskeleton to play important role in regulating signal transduction pathways[15,16,17,18,19,20]. These proteins are highly conserved throughout evolution, at their N- and C-terminus regions[21,22,23,24,25], and expressed in a tissue-specific manner[11,26]. Illumina midseq lung cancer cells, directly binds to phosphorylated ERM (p-ERM) and play a critical role in ERM activation

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Results

Conclusion