Differential mRNA stability to reticulocyte ribonucleases correlates with 3' non-coding (U)nA sequences.
The stabilities of different mRNA species were analyzed in a reticulocyte lysate system under protein-synthesizing conditions. In all cases examined the relative mRNA degradation by reticulocyte ribonucleases as well as by the interferon-modulated (2'-5') (A)n-dependent endonuclease correlated with the extent of (U)nA sequences within the 3' non-coding region. The experimental data presented indicate that according to their stabilities at least three major mRNA groups may be identified: (a) (U)nA-poor mRNAs (e.g. globin) are essentially stable and are only slightly degraded by the (2'-5')(A)n-dependent endonuclease; (b) mRNA species with intermediate (U)nA levels (e.g. Ig alpha and Ig mu heavy-chain mRNAs) are partially degraded by general ribonuclease activity and further degraded by the (2'-5')(A)n-dependent endonuclease and (c) (U)nA-rich mRNA species (such as c-myc and non-skeletal actin mRNAs) are inherently unstable and are extremely sensitive to degradation by general ribonuclease activity. A survey of mRNA nucleotide sequences demonstrated that without exception (U)nA-rich stretches appeared more frequently within the 3' non-coding region than in the coding or 5' non-coding regions. A comparison of 3' non-coding region sequences from 92 different mRNAs revealed that transiently expressed mRNAs, such as the interleukins, nerve growth factor, epidermal growth factor receptor, c-myc, c-fos, c-myb and several other oncogenes as well as interferons alpha, beta and gamma were exceptionally (U)nA-rich. It is postulated that differential mRNA stability may be partly determined by the primary nucleotide sequence and in particular by (U)nA sequences within the 3' non-coding region. This may represent a novel post-transcriptional strategy employed by the cell to selectively retain or destroy discrete mRNA species.
Wreschner
D H
DH
Department of Microbiology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Rechavi
G
G
D000818:Animals; D002417:Cattle; D004722:Endoribonucleases / Q000378:metabolism; D005815:Genetic Code; D006801:Humans; D051379:Mice; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012156:Reticulocytes / Q000201:enzymology*; D012260:Ribonucleases / Q000378:metabolism*
D012333:RNA, Messenger; C033547:2'-5'-oligo(A)-dependent endonuclease; D004722:Endoribonucleases; D012260:Ribonucleases