Tissue- and age-dependent expression of RNA-binding proteins that influence mRNA turnover and translation.
Gene expression patterns vary dramatically in a tissue-specific and age-dependent manner. RNA-binding proteins that regulate mRNA turnover and/or translation (TTR-RBPs) critically affect the subsets of expressed proteins. However, very little is known regarding the tissue- and age-dependent expression of TTR-RBPs in humans. Here, we use human tissue arrays containing a panel of organ biopsies from donors of different ages, to study the distribution and abundance of four TTR-RBPs: HuR, AUF1, TIA-1, and TTP. HuR and AUF1 were expressed with remarkably similar patterns. Both TTR-RBPs were present in high percentages of cells and displayed elevated intensities in many age groups and tissues, most notably in the gastrointestinal and reproductive systems; they were moderately expressed in the urinary and immune systems, and were almost undetectable in muscle and brain. TIA-1 was also abundant in many tissues and age groups; TIA-1 was expressed at high levels in the gastrointestinal, immune, urinary, and reproductive systems, and at low levels in brain and muscle. By contrast, TTP-expressing cells, as well as TTP signal intensities declined with advancing age, particularly in the immune, nervous, and muscular systems; however, TTP levels remained elevated in the gastrointestinal tract. The widespread abundance of HuR, AUF1, and TIA-1 throughout the body and in all age groups was in stark contrast with their declining levels in human diploid fibroblasts (HDFs) undergoing replicative senescence, a cultured-cell model of aging. Conversely, TTP levels increased in senescent HDFs, while TTP levels decreased with advancing age. Our studies provide a framework for the study of human TTR-RBP function in different tissues, throughout the human life span.
Laboratory of Cellular and Molecular Biology, NIA-IRP, NIH, Baltimore, MD 21224, USA.
Kiyoshi
K
Masuda
Bernard
B
Marasa
Jennifer L
JL
Martindale
Marc K
MK
Halushka
Myriam
M
Gorospe
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism; D020869:Gene Expression Profiling; D005835:Genitalia / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014018:Tissue Distribution; D014551:Urinary Tract / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D016601:RNA-Binding Proteins