Tissue- and age-dependent expression of RNA-binding proteins that influence mRNA turnover and translation - PubMed (original) (raw)

Tissue- and age-dependent expression of RNA-binding proteins that influence mRNA turnover and translation

Kiyoshi Masuda et al. Aging (Albany NY). 2009.

Abstract

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.

Keywords: AUF1; HuR; TIA-1; TTP; TTR-RBPs; senescence.

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Conflict of interest statement

The authors of this manuscript have no conflict of interests to declare.

Figures

Figure 1.

Figure 1.. TTR-RBP expression in WI-38 human diploid fibroblasts (HDFs).

WI-38 HDFs were cultured for extended population doublings (pdls), until they reached senescence at ~pdl 52. The abundance of TTR-RBPs HuR, AUF1 (all four isoforms indicated), TIA-1, and TTP was assessed by Western blot analysis. GAPDH signals were included as a loading control.

Figure 2.

Figure 2.. Immunohistochemical detection of HuR across tissue types and age groups.

Representative HuR signals in photomicrographs taken from the indicated tissue sections from human tissue arrays. Images are shown at ×200 magnification.

Figure 3.

Figure 3.. Immunohistochemical detection of AUF1 across tissue types and age groups.

Representative AUF1 signals in photomicrographs taken from the indicated tissue sections from human tissue arrays. Images are shown at ×200 magnification.

Figure 4.

Figure 4.. Immunohistochemical detection of TIA-1 across tissue types and age groups.

Representative TIA-1 signals in photomicrographs taken from the indicated tissue sections from human tissue arrays. Images are shown at ×200 magnification.

Figure 5.

Figure 5.. Immunohistochemical detection of TTP across tissue types and age groups.

Representative TTP signals in photomicrographs taken from the indicated tissue sections from human tissue arrays. Images are shown at ×200 magnification.

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