Study of RNA Turnover in mammalian cells

Abstract

Enormous number of examples known till date of mammalian genes whose expression is newlineregulated by controlling the rate of degradation of their mRNAs emphasizes the importance of newlinemRNA turnover process in gene expression in mammals. However, the mechanism of the newlineturnover process is unclear to a large extent. Knowledge about various factors involved in newlineregulated mRNA turnover is still limiting - some cis-acting elements mediating the process have newlinebeen identified but ribonucleases and other trans-acting factors involved are poorly understood. newlineThe broad objective of this study, therefore, was to gain some insight into the nature of the newlinemachinery involved in mRNA degradation in mammalian cells. Two approaches were taken to newlinethis end. newline(a) The first approach was to characterize the in vivo generated degradation intermediates (Dis) newlineof an mRNA and the cleavages which give rise to them in order to obtain information on the newlinenucleases involved in the process. Albumin mRNA is an abundantly expressed stable newlinemessage whose expression has been extensively studied in rodents and is known to get newlineregulated during development both in rat and mouse. Albumin (though known to be a liver newlinespecific protein), is expressed in rat even in many of the nonhepatic fetal tissues. The newlineabundance of albumin mRNA may enable relatively easy detection of its in vivo Dis, if any; newlinehowever, such studies have not been reported. Therefore, the study of the expression and newlinecleavages of mouse albumin mRNA in relation to liver development and the nature of cell newlinetype was undertaken. newline(b) Another independent approach involved the study of mammalian cytosolic neutral RNase newlineactivity to understand the mechanism of its regulation and the role of cytosolic RNase newlineinhibitor (RI) in that process. Several studies have been attempted in the past to understand newlinethe relationship between cellular RNA turnover and the cytosolic RNase/RI system. newlineHowever, it is yet to be understood fully.