A phosphorylation-wide sncRNA screen reveals Protein Functional Effector sncRNAs (pfeRNAs) in human lung somatic cells.
We recently reported that PIWI-interacting RNAs likes (piR-Ls) could regulate functions of the interacting phosphorylated proteins (p-Proteins). In addition, except for writers and erasers, functional efficacy of p-Proteins on their readers still remains unknown. We, therefore, reasoned there was a type of sncRNAs which could regulate functional efficacy of p-Proteins. Here, we profiled sncRNAs interacting with phosphorylated -Ser, -Thr and -Tyr residues in 3 HBE and 4 lung SCC cell lines, investigated effects and mechanisms of phosphorylated-residue-interacting sncRNAs. Our results demonstrated sncRNAs regulating functional efficacy of p-Proteins and we thus referred them as Protein Functional Effector sncRNAs (pfeRNAs). pfeRNAs were distributed among 26 to 50 nucleotides, shared some core sequences and showed distinctive expression patterns between HBE and SCC cells. Core sequences 417 (CS417), showing consistent upregulation in all 4 SCC cells, bound directly to p-Nucleolin (NCL), which was dependent on the key elements CGCG of CS417 and p-Ser619 of NCL. The CS417/p-NCL interaction was critical for functional efficacy of p-NCL in basic activities of lung normal and cancer cells. Thus, we revealed a novel type of pfeRNAs controlling functional efficacy of p-Proteins in lung somatic cells.
Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, University of Maryland, 650 W Baltimore St, Baltimore, MD, 21201, USA.
Tyler
T
Gable
Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, University of Maryland, 650 W Baltimore St, Baltimore, MD, 21201, USA; Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Beijing Institute for Cancer Research, Beijing, 100142, China.
Yuyan
Y
Wang
Department of Pathology, Johns Hopkins University, Baltimore, MD, 21287, USA.
David
D
Clark
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Priti
P
Kumari
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Amol Carl
AC
Shetty
Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, University of Maryland, 650 W Baltimore St, Baltimore, MD, 21201, USA.
Mao
M
Li
Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, University of Maryland, 650 W Baltimore St, Baltimore, MD, 21201, USA. Electronic address: ymei@umaryland.edu.
Yuping
Y
Mei
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D058727:RNA, Small Untranslated / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D058727:RNA, Small Untranslated
Lung squamous cell carcinoma; Phosphorylated proteins; Protein Functional Effector sncRNAs (pfeRNAs); sncRNAs