Intrusion of a DNA Repair Protein in the RNome World: Is This the Beginning of a New Era?

Abstract

Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is known to be involved in base excision DNA repair, acting as the major abasic endonuclease; the protein also functions as a redox coactivator of several transcription factors that regulate gene expression. Recent findings highlight a novel role for APE1 in RNA metabolism. The new findings are as follows: (i) APE1 interacts with rRNA and ribosome processing protein NPM1 within the nucleolus; (ii) APE1 interacts with proteins involved in ribosome assembly (i.e., RLA0, RSSA) and RNA maturation (i.e., PRP19, MEP50) within the cytoplasm; (iii) APE1 cleaves abasic RNA; and (iv) APE1 cleaves a specific coding region of c-myc mRNA in vitro and influences c-myc mRNA level and half-life in cells. Such findings on the role of APE1 in the posttranscriptional control of gene expression could explain its ability to influence diverse biological processes and its relocalization to cytoplasmic compartments in some tissues and tumors. In addition, we propose that APE1 serves as a “cleansing” factor for oxidatively damaged abasic RNA, establishing a novel connection between DNA and RNA surveillance mechanisms. In this review, we introduce questions and speculations concerning the role of APE1 in RNA metabolism and discuss the implications of these findings in a broader evolutionary context.

We regret the omission of many important references due to space limitations.

This work was supported by grants from MIUR (FIRB RBRN07BMCT_008) to G.T., NSERC Discovery Grant (grant no. 227158) to C.H.L., and the Intramural Research Program of NIH, National Institute on Aging to D.M.W.

Additional information

Notes on contributors

Gianluca Tell

Prof. Gianluca Tell is Associate Professor of Molecular Biology at the School of Medicine—University of Udine (UNIUD), Italy. He obtained his Ph.D. from the University of Trieste in Italy and was a visiting scientist in 1996 at the NCI, NIH, Bethesda, MD. His prevailing scientific interest is the study of molecular mechanisms of gene expression in the field of redox signaling and cell oxidative stress. In the last 10 years he devoted himself to the study of the role of the protein APE1 in transcriptional regulation in different cell models and human cancers, discovering a new unsuspected role for this protein in RNA metabolism and coordinating several research projects on these topics. He authored more than 100 publications in international peer-reviewed journals. Before joining UNIUD, he was an Assistant Professor at the University of Trieste and visiting professor in 2006 at the UTMB, Galveston, TX.

David M. Wilson

Dr. David M. Wilson III received a bachelor of arts degree in both biology and political science from Bucknell University in 1989. He completed his Ph.D. work in 1993 at Loyola University of Chicago, Stritch School of Medicine, as part of the Molecular Biology Program. Dr. Wilson performed his postdoctoral training at the Harvard School of Public Health until 1997, when he became a Senior Biomedical Scientist at Lawrence Livermore National Laboratory in the Biology and Biotechnology Research Program. While at Livermore, he was briefly an adjunct faculty member in the Radiation Oncology Department at the University of California Cancer Center—Sacramento. Dr. Wilson started at the National Institute on Aging Intramural Research Program in the Laboratory of Molecular Gerontology in 2002 and became a tenured Senior Investigator in 2008. He has been working on specific aspects of base excision DNA repair since a graduate student.

Chow H. Lee

Dr. Chow H. Lee is an Associate Professor in the Chemistry Program, College of Science and Management, at the University of Northern British Columbia, Prince George, BC, Canada. He has been working on endoribonucleases and their role in the control of mRNA turnover and gene expression as it relates to cancer since 1996. Before joining the University of Northern British Columbia in 1998, Dr. Lee spent his postdoctoral research work at the Ontario Cancer Institute, BC Cancer Agency, and McArdle Laboratory for Cancer Research, University of Wisconsin—Madison. Dr. Lee obtained his Ph.D. from Flinders University in 1992 and his B.Sc. with first class honors from the University of New South Wales in 1988, both in Australia. Using biochemical purification techniques, he fortuitously discovered APE1 as an endoribonuclease that cleaves c-myc mRNA in vitro and regulates c-myc mRNA level and stability in cells.