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

Masuda K, Marasa B, Martindale JL, Halushka MK, Gorospe M - Aging (Albany NY) (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Biology, NIA-IRP, NIH, Baltimore, MD 21224, USA.

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.

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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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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.

Mentions: Like TIA-1, the numbers of TTP-expressing cells were highest in the fetal (F) group, generally decreasing in older groups (Table 4, left columns). Exceptions to this pattern were the GI and endocrine systems, where TTP-positive cell numbers remained constant across age groups, and the reproductive tissues, where TTP-positive cells increased with advancing age. TTP intensities also generally declined across tissue types when examining progressively older donors (Table 4, right columns). Representative micrographs from the GI and immune systems are shown (Figure 5). The dis-agreement between replicative senescence and in vivo aging was also seen with TTP, as senescent cells expressed increasingly higher TTP, while advancing age progressively lowered the number of TTP-expressing cells and TTP abundance per cell. Although TTP levels can be induced by a variety of stimuli, the constitutive TTP expression decreased markedly with advancing age.


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

Masuda K, Marasa B, Martindale JL, Halushka MK, Gorospe M - Aging (Albany NY) (2009)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806049&req=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.
Mentions: Like TIA-1, the numbers of TTP-expressing cells were highest in the fetal (F) group, generally decreasing in older groups (Table 4, left columns). Exceptions to this pattern were the GI and endocrine systems, where TTP-positive cell numbers remained constant across age groups, and the reproductive tissues, where TTP-positive cells increased with advancing age. TTP intensities also generally declined across tissue types when examining progressively older donors (Table 4, right columns). Representative micrographs from the GI and immune systems are shown (Figure 5). The dis-agreement between replicative senescence and in vivo aging was also seen with TTP, as senescent cells expressed increasingly higher TTP, while advancing age progressively lowered the number of TTP-expressing cells and TTP abundance per cell. Although TTP levels can be induced by a variety of stimuli, the constitutive TTP expression decreased markedly with advancing age.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Biology, NIA-IRP, NIH, Baltimore, MD 21224, USA.

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.

Show MeSH