Microarrays and the relationship of mRNA variation to protein variation during the cell cycle.
Microarray analyses have led to the postulated existence and identification of numerous genes that are believed to be expressed and presumably to act in a cell-cycle-specific manner because their expression varies during the cell cycle. It is important to see how protein variation can be produced from mRNA variation. We have calculated the protein content throughout the cell cycle resulting from cell-cycle-specific mRNA expression, and compared the result to protein content resulting from constant, cell-cycle independent, mRNA expression. For stable proteins, cell-cycle-specific mRNA expression leads to a maximum 2-fold change in protein content compared to proteins synthesized from constantly expressed mRNA. More realistic sinusoidal patterns of mRNA expression exhibit much smaller ratios of 1.25 or lower, even for extremely large amplitudes in mRNA expression. For unstable proteins that have a cycle-independent half-life, only at extremely short protein half-lives does mRNA variation have a significant impact on variation of protein content during the division cycle. We also apply these findings to proteins with a cycle-specific decay pattern. mRNA variations during the eukaryotic division cycle variation of mRNA during the cell cycle can have only a minimal affect on the variation of protein content during the cell cycle. We conclude that mRNA variations during the division cycle, as measured by microarrays, cannot by themselves, identify cycle-specific functions related to protein variations.
Cooper
Stephen
S
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA. cooper@umich.edu
Shedden
Kerby
K
D000818:Animals; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*
D018797:Cell Cycle Proteins; D012333:RNA, Messenger