RNA-Binding Proteins

Publication Title: 
The Journal of Biological Chemistry

In lower organisms, increased expression of the NAD-dependent deacetylase Sir2 augments lifespan. The mechanism through which this life extension is mediated remains incompletely understood. Here we have examined the cellular effects of overexpression of SIRT1, the closest mammalian ortholog of Sir2. In PC12 cells, increased expression of the NAD-dependent deacetylase SIRT1 reduces cellular oxygen consumption by approximately 25%. We further demonstrate that SIRT1 expression can alter the transcriptional activity of the mitochondrial biogenesis coactivator PGC-1alpha.

Author(s): 
Nemoto, Shino
Fergusson, Maria M.
Finkel, Toren
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The burden of protein misfolding is believed to contribute to aging. However, the links between adaptations to conditions associated with protein misfolding and resistance to the time-dependent attrition of cellular function remain poorly understood. We report that worms lacking aip-1, a homologue of mammalian AIRAP (arsenic-inducible proteasomal 19S regulatory particle-associated protein), are not only impaired in their ability to resist exposure to arsenite but also exhibit shortened lifespan and hypersensitivity to misfolding-prone proteins under normal laboratory conditions.

Author(s): 
Yun, Chi
Stanhill, Ariel
Yang, Yun
Zhang, Yuhong
Haynes, Cole M.
Xu, Chong-Feng
Neubert, Thomas A.
Mor, Adam
Philips, Mark R.
Ron, David
Publication Title: 
Aging Cell

Coordinated expression of mitochondrial and nuclear genes is required to maintain proper mitochondrial function. However, the precise mechanisms that ensure this coordination are not well defined. We find that signaling from mitochondria to the nucleus is influenced by mammalian target of rapamycin (mTOR) activity via changes in autophagy and p62/SQSTM1 turnover. Reducing mTOR activity increases autophagic flux, enhances mitochondrial membrane potential, reduces reactive oxygen species within the cell, and increases replicative life span.

Author(s): 
Lerner, Chad
Bitto, Alessandro
Pulliam, Daniel
Nacarelli, Timothy
Konigsberg, Mina
Van Remmen, Holly
Torres, Claudio
Sell, Christian
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Cellular quiescence is a reversible cell cycle arrest that is poised to re-enter the cell cycle in response to a combination of cell-intrinsic factors and environmental cues. In hematopoietic stem cells, a coordinated balance between quiescence and differentiating proliferation ensures longevity and prevents both genetic damage and stem cell exhaustion. However, little is known about how all these processes are integrated at the molecular level.

Author(s): 
Yamada, Takeshi
Park, Chun Shik
Lacorazza, H. Daniel
Publication Title: 
Biogerontology

It is known that a global decrease in food ingestion (dietary restriction, DR) lowers mitochondrial ROS generation (mitROS) and oxidative stress in young immature rats. This seems to be caused by the decreased methionine ingestion of DR animals. This is interesting since isocaloric methionine restriction in the diet (MetR) also increases, like DR, rodent maximum longevity.

Author(s): 
Sanchez-Roman, Ines
GÛmez, Alexia
PÈrez, Irene
Sanchez, Carlota
Suarez, Henar
Naudí, Alba
Jové, Mariona
Lopez-Torres, MÛnica
Pamplona, Reinald
Barja, Gustavo
Publication Title: 
The Journal of Cell Biology

Telomeres are the protein-nucleic acid structures at the ends of eukaryote chromosomes. Tandem repeats of telomeric DNA are templated by the RNA component (TER1) of the ribonucleoprotein telomerase. These repeats are bound by telomere binding proteins, which are thought to interact with other factors to create a higher-order cap complex that stabilizes the chromosome end.

Author(s): 
Smith, C. D.
Blackburn, E. H.
Publication Title: 
Biological Psychiatry

BACKGROUND: A number of studies have suggested deficits in myelination and glial gene expression in different psychiatric disorders. We examined the brain expression and genetic/epigenetic regulation of QKI, an oligodendrocyte-specific RNA binding protein important for cell development and myelination. METHODS: The microarray-based expression of QKI was evaluated in cortical and subcortical brain regions from suicide victims with a diagnosis of major depression (n = 16) and control subjects (n = 13).

Author(s): 
Klempan, Timothy A.
Ernst, Carl
Deleva, Vesselina
LabontÈ, Benoit
Turecki, Gustavo
Publication Title: 
Molecular Psychiatry

Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene-environment interactions underlying complex behavior in health and disease.

Author(s): 
Eran, A.
Li, J. B.
Vatalaro, K.
McCarthy, J.
Rahimov, F.
Collins, C.
Markianos, K.
Margulies, D. M.
Brown, E. N.
Calvo, S. E.
Kohane, I. S.
Kunkel, L. M.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Ashwagandha is an Ayurvedic shrub that forms a common ingredient of health supplements, tonics, and Indian home remedies designed to promote health and quality of life. Though sustained through experience and history, there are only a limited laboratory studies and experimental evidence to its effects. In our efforts to characterize Ashwagandha activities and their molecular mechanisms, we initially prepared leaf extract of Ashwagandha (i-Extract) that showed tumor-inhibitory activity.

Author(s): 
Widodo, Nashi
Shah, Navjot
Priyandoko, Didik
Ishii, Tetsuro
Kaul, Sunil C.
Wadhwa, Renu
Publication Title: 
Molecular Biology of the Cell

Maintenance of intestinal mucosal epithelial integrity requires polyamines that modulate the expression of various genes involved in cell proliferation and apoptosis. Recently, polyamines were shown to regulate the subcellular localization of the RNA-binding protein HuR, which stabilizes its target transcripts such as nucleophosmin and p53 mRNAs. The activating transcription factor-2 (ATF-2) mRNA encodes a member of the ATF/CRE-binding protein family of transcription factors and was computationally predicted to be a target of HuR.

Author(s): 
Xiao, Lan
Rao, Jaladanki N.
Zou, Tongtong
Liu, Lan
Marasa, Bernard S.
Chen, Jie
Turner, Douglas J.
Zhou, Huiping
Gorospe, Myriam
Wang, Jian-Ying

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