Differential Alterations in Metabolic Pattern of the Spliceosomal Uridylic Acid-Rich Small Nuclear RNAs (UsnRNAs) During Malignant Transformation of 20-Methylcholanthrene-induced Mouse CNCI-PM-20 Embryonic Fibroblasts

Differential alterations of the spliceosomal Uridylic acid rich small nuclear RNAs (UsnRNAs) (U1, U2, U4, US, and U6) are reported to be associated with cellular proliferation and development, but definitive information is scarce and also elusive. An attempt is made in this study to analyze the metabolic patterns of major spliceosomal UsnRNAs, during tumor development, in an in vitro carcinogenesis model of 20-methylcholanthrene (MCA)-transformed Swiss Mouse Embryonic Fibroblast (MEF), designated as CNCI-PM-20. MEF cells, after treatment with 20-MCA, progressed through a sequence of passages with distinct and heritable changes, finally becoming neoplastic at passage-42 (P42). A differential expression pattern of major UsnRNAs was observed during this process. The abundance of U1 was 20% below control (P1) at passage-20 (P20), followed by a gradual increase up until P42 (similar to 12% above the P1 value). The abundance of U2 was more or less constant during the cellular transformation. U4 showed a trend of increase, with above 30% abundance than control at P20, followed by a significant increase at P36 and P42 (1.5- and 2-fold, respectively, P-value <0.01). US also followed an identical pattern, with an increase of 70% compared to control (P-value <0.05) at P42. Interestingly, U6 gradually decreased from P20 onwards up until P42, with 22% at P20 and 67% at P42 (P-value <0.01). An overall significant quantitative alteration in abundance of U4, US, and U6, observed in our study, contributes to the understanding of the fact that, the metabolism of major spliceosomal UsnRNAs is differentially regulated during the process of neoplastic transformation. (C) 2009 Wiley-Liss, inc.