RNA Processing, Post-Transcriptional

Publication Title: 
BMC genomics

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. RESULTS: We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity.

Author(s): 
Gombar, Saurabh
Jung, Hwa Jin
Dong, Feng
Calder, Brent
Atzmon, Gil
Barzilai, Nir
Tian, Xiao-Li
Pothof, Joris
Hoeijmakers, Jan H. J.
Campisi, Judith
Vijg, Jan
Suh, Yousin
Publication Title: 
BMC genomics

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. RESULTS: We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity.

Author(s): 
Gombar, Saurabh
Jung, Hwa Jin
Dong, Feng
Calder, Brent
Atzmon, Gil
Barzilai, Nir
Tian, Xiao-Li
Pothof, Joris
Hoeijmakers, Jan H. J.
Campisi, Judith
Vijg, Jan
Suh, Yousin
Publication Title: 
Molecular and Cellular Biology

The AU-rich elements (AREs) encoded within many mRNA 3' untranslated regions (3'UTRs) are targets for factors that control transcript longevity and translational efficiency. Hsp70, best known as a protein chaperone with well-defined peptide-refolding properties, is known to interact with ARE-like RNA substrates in vitro. Here, we show that cofactor-free preparations of Hsp70 form direct, high-affinity complexes with ARE substrates based on specific recognition of U-rich sequences by both the ATP- and peptide-binding domains.

Author(s): 
Kishor, Aparna
Tandukar, Bishal
Ly, Yann V.
Toth, Eric A.
Suarez, Yvelisse
Brewer, Gary
Wilson, Gerald M.
Publication Title: 
Aging

The Editorial Board of Aging reviews research papers published in 2009, which they believe have or will have significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacological interventions into aging.

Author(s): 
Blagosklonny, Mikhail V.
Campisi, Judy
Sinclair, David A.
Bartke, Andrzej
Blasco, Maria A.
Bonner, William M.
Bohr, Vilhelm A.
Brosh, Robert M.
Brunet, Anne
DePinho, Ronald A.
Donehower, Lawrence A.
Finch, Caleb E.
Finkel, Toren
Gorospe, Myriam
Gudkov, Andrei V.
Hall, Michael N.
Hekimi, Siegfried
Helfand, Stephen L.
Karlseder, Jan
Kenyon, Cynthia
Kroemer, Guido
Longo, Valter
Nussenzweig, Andre
Osiewacz, Heinz D.
Peeper, Daniel S.
Rando, Thomas A.
Rudolph, K. Lenhard
Sassone-Corsi, Paolo
Serrano, Manuel
Sharpless, Norman E.
Skulachev, Vladimir P.
Tilly, Jonathan L.
Tower, John
Verdin, Eric
Vijg, Jan
Publication Title: 
Cold Spring Harbor Symposia on Quantitative Biology

Telomeres are maintained by the ribonucleoprotein (RNP) enzyme telomerase, which replenishes telomeres through its unique mechanism of internal RNA-templated addition of telomeric DNA. Telomerase is active in most human cancers, typically because its core protein subunit, TERT, is up-regulated. Although the major known function of telomerase in cancer is to replenish telomeric DNA and maintain cell immortality, the regulation of the RNA component of telomerase is not well understood.

Author(s): 
Li, S.
Blackburn, E. H.
Publication Title: 
Genes & Development

The ribonucleoprotein enzyme telomerase adds telomeric DNA to chromosomal ends. In most eukaryotes the telomeric repeat units are repeated precisely, consistent with the action of a telomerase that faithfully copies its RNA template. In contrast, Saccharomyces cerevisiae telomeric repeats are degenerate, suggesting that its telomerase has unusual mechanistic properties. We mutated the S. cerevisiae telomerase RNA (TLC1) with a series of 3-base (GUG) substitutions in and next to the 17-nucleotide templating domain.

Author(s): 
Prescott, J.
Blackburn, E. H.
Publication Title: 
Neurobiology of Disease

Cortical and subcortical dysfunction in schizophrenia includes altered expression of RNA and proteins involved in neurotransmission, metabolism, myelination and other functions. The molecular mechanisms underlying this type of alteration remain largely unknown. Here, we summarize findings from postmortem brain studies and argue that transcriptional dysregulation, including changes in DNA and histone modifications involved in epigenetic control of gene expression, as well as microRNA-mediated post-transcriptional mechanisms contribute to the neurobiology of schizophrenia.

Author(s): 
Gavin, David P.
Akbarian, Schahram
Publication Title: 
Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration

The identification of genetic and epigenetic factors that are associated with an increased risk of developing amyotrophic lateral sclerosis (ALS), or that modify the age of onset or rate of progression, requires a multimodal research strategy, facilitated through international collaboration. The discovery of several ALS genes strongly linked to RNA biology, the proteasome pathway, and axonal transport suggest they have an important role in pathogenesis, but the immense complexity of these processes is also apparent.

Author(s): 
Al-Chalabi, Ammar
Kwak, Shin
Mehler, Mark
Rouleau, Guy
Siddique, Teepu
Strong, Michael
Leigh, Peter Nigel
Publication Title: 
Advanced Drug Delivery Reviews

Long non-coding RNAs (lncRNA), a class of non-coding RNA molecules recently identified largely due to the efforts of FANTOM, and later GENCODE and ENCODE consortia, have been a subject of intense investigation in the past decade. Extensive efforts to get deeper understanding of lncRNA biology have yielded evidence of their diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation and epigenetic regulation.

Author(s): 
Khorkova, O.
Hsiao, J.
Wahlestedt, C.
Publication Title: 
BMC genomics

BACKGROUND: FUS (TLS) and EWS (EWSR1) belong to the FET-protein family of RNA and DNA binding proteins. FUS and EWS are structurally and functionally related and participate in transcriptional regulation and RNA processing. FUS and EWS are identified in translocation generated cancer fusion proteins and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.

Author(s): 
Luo, Yonglun
Blechingberg, Jenny
Fernandes, Ana Miguel
Li, Shengting
Fryland, Tue
B¯rglum, Anders D.
Bolund, Lars
Nielsen, Anders Lade

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