Gender	Male
E-mail	david.bechhofer@mssm.edu
Awards	2007 NIH Microbial Genetics Study Section
	2004 NIH Microbial Genetics Study Section
	1993 NIH Microbial Genetics Study Section
	1984 - 1986 USPHS Postdoctoral Fellowship Award (GM09853)
	1978 Max Pavey Award for Excellence in Chemistry
	1978 - 1979 USPHS Predoctoral Training Grant (AI07161)

Dr. Bechhofer received his undergraduate degree in Biochemistry from City College of New York (CUNY) in 1978. His thesis research as a graduate student at Columbia University, Department of Microbiology, focused on maintenance of the broad-host-range plasmid, RK2. After receiving a Ph.D. degree from Columbia in 1984, Dr. Bechhofer went on to postdoctoral studies in the laboratory of Dr. David Dubnau at the Public Health Research Institute of New York, where he was introduced to the subject that remains the focus of his research efforts: regulation of mRNA stability in Bacillus subtilis. Dr. Bechhofer joined Mount Sinai as an Assistant Professor in 1986. Research in his laboratory has been funded by the NIH since 1987. He was appointed Associate Professor in 1993, and Professor in 2008 jointly in the Department of Pharmacology and Systems Therapeutics and the Department of Medical Education. Since 2001, Dr. Bechhofer has been director of the first-year medical school “Molecules and Cells” course, which covers basic biochemistry, cell and molecular biology, electrophysiology, and metabolism.

Bechhofer Laboratory Website

Specific Clinical/Research Interests:
Prokaryotic mRNA decay and stable RNA processing

Postdoctoral Fellows: Gintaras Deikus, Shiyi Yao

Summary of Research Studies:
The mechanism of RNA processing, and particularly messenger RNA decay, in the Gram-positive bacterium Bacillus subtilis is the major focus of our laboratory. Previous studies concentrated on an inducibly stable mRNA- the mRNA encoded by the erythromycin-resistance gene, ermC. Numerous derivatives of ermC mRNA have been constructed, and these remain useful tools to probe the mechanism of mRNA decay. We have shown that the 5' end of a message plays an important role in determining mRNA half-life, and are currently looking at specific sites on the mRNA at which decay initiates.

Several genes encoding ribonucleases have been cloned, including four genes encoding 3'-to-5' exonucleases and one gene encoding a narrow-specificity endonuclease (called "Bs-RNase III"). In order to understand the function of these exonucleases, we are analyzing decay of endogenous mRNAs in mutant strains lacking one or more of these genes. We are concentrating on small, monocistronic mRNAs, as these are amenable to detailed analysis and likely provide few sites for initiation of decay. Functional homologues for three of the major players in E. coli mRNA decay- RNase E, RNase II, and oligoribonuclease- have so far not been identified in B. subtilis. A combination of genetic and biochemical approaches is being pursued to identify new B. subtilis genes that are involved in RNA processing. A major goal is to discover the 5'-end-dependent endonuclease that is believed to initiate mRNA decay. Another major goal is to identify other exoribonuclease activities, since a mutant strain missing all four of the currently known exonucleases is viable and clearly contains one or more other 3'-to-5' exonuclease activities.

Ongoing projects in the lab and in collaboration with other laboratories, include:

-The effect of polyadenylation on mRNA decay. We have demonstrated that B. subtilis mRNA is polyadenylated, but the identity of the B. subtilis poly(A) polymerase has been a mystery. Biochemical purification of a poly(A) polymerase activity is anticipated, which will be followed by genetic studies of a strain lacking this activity.

-Endoribonuclease cleavage at a site of ribosome stalling. We have new evidence that RNase J1, a novel endonuclease that was discovered recently, is likely responsible for such cleavage activity. The physiological relevance of mRNA cleavage in response to ribosome stalling is being investigated.

-Basis for essential nature of Bs-RNase III. Strains lacking this activity are non-viable, but the basis for this is not known. A rare strain that is missing Bs-RNase III has been recovered, and this strain presumably contains a secondary mutation that compensates for the missing crucial Bs-RNase III activity.

For more information, please visit the Bechhofer Laboratory website.

Cardenas PP, Carrasco B, Sanchez H, Deikus G, Bechhofer DH, Alonso JC. Bacillus subtilis polynucleotide phosphorylase 3'-to-5' DNase activity is involved in DNA repair. Nucleic Acids Res 2009 Jul; 37(12): 4157-4169.

Bechhofer DH. Messenger RNA decay and maturation in Bacillus subtilis. Prog Mol Biol Transl Sci 2008; 85: 231-273.

Condon C, Pellegrini O, Mathy N, Benard L, Redko Y, Oussenko IA, Deikus G, Bechhofer DH. Assay of Bacillus subtilis ribonucleases in vitro. Methods Enzymol 2008; 447: 277-308.

Bechhofer DH, Oussenko IA, Deikus G, Yao S, Mathy N, Condon C. Analysis of mRNA decay in Bacillus subtilis. Methods Enzymol. 2008; 447: 259-276.

Yao S, Blaustein JB, Bechhofer DH. Erythromycin-induced ribosome stalling and RNase J1-mediated mRNA processing in Bacillus subtilis.. Mol Microbiol 2008 Sep; 69(6): 1439-1449.

Deikus G, Condon C, Bechhofer DH. Role of Bacillus subtilis RNase J1 endonuclease and 5'-exonuclease activities in trp leader RNA turnover. J Biol Chem 2008 Jun; 283(25): 17158-17167.

Redko Y, Bechhofer DH, Condon C. Mini-III, an unusual member of the RNase III family of enzymes, catalyses 23S ribosomal RNA maturation in B. subtilis. Mol Microbiol 2008 Jun; 68(5): 1096-1106.

Yao S, Blaustein JB, Bechhofer DH. Processing of Bacillus subtilis small cytoplasmic RNA: evidence for an additional endonuclease cleavage site. Nucleic Acids Res 2007 Jun; 35(13): 4464-4473.

Deikus G, Bechhofer DH. Initiation of decay of Bacillus subtilis trp leader RNA. J Biol Chem 2007 Jul; 282(28): 20238-20244.

Wei Y, Deikus G, Powers B, Shelden V, Krulwich TA, Bechhofer DH. Adaptive gene expression in Bacillus subtilis strains deleted for tetL. J Bacteriol 2006 Oct; 188(20): 7090-7100.