Nicholas Delihas

E-mail:
Office:

nicholas.delihas@stonybrook.edu
(631) 286-9427

Publications

Journal Editorial Boards:

International Journal of Molecular Sciences, Editorial Board Member
Biochemistry, Molecular and Cellular Biology, Section Board Editor
Molecular Biophysics, Section Board Member
Non-Coding RNA, Editorial Board Member

Past Research

Control of gene expression: Characterization of the first discovered regulatory RNA gene, the micF gene, and determination of its transcript functions

During past decades, our research concentrated on elucidation of transcriptional activation and suppression of the regulatory non-coding micF RNA gene, characterization of its RNA transcript and determination of functional role of the RNA. The micF gene was first discovered and proposed to regulate gene expression by Dr. Masayori Inouye and Dr. Takeshi Mizuno in the early 1980s. Our lab subsequently characterized the micF gene, found and characterized its RNA transcript, showed that it binds the target ompF mRNA, determined the MicF RNA/ target ompF mRNA duplex structure (figure below) and showed the RNA functions as a regulator of gene expression in response to cellular internal and environmental stress conditions. Former graduate student Dr. Janet Andersen played a major role in these determinations. MicF RNA has the distinction of being the first non-coding regulatory RNA to have been proposed and characterized. Other labs, led by Dr. Gerhart Wagner in Sweden and Dr. Jorg Vogel in Germany have shown a greatly expanded role in cell physiology whereby multiple target genes are regulated by micF, including a global regulator that controls ~10% of all protein genes (Mol. Microbiol (2012) 84:414 and 428). The initial findings on MicF RNA opened the door to revealing a major principle of biology: the regulation of gene expression by RNA.

First determination of a regulatory non-coding RNA/target mRNA duplex interaction by structure probing determined by Dr. Matthew Schmidt, former graduate student (Schmidt, M., et al., 1995).

Current Research

Research efforts have now expanded to analysis of human long non-coding RNA (lncRNA) genes and transcripts. lncRNAs are a diverse class of eukaryotic RNAs that have a chain  length greater then 200 nucleotides. It is known that the human genome consists of tens of thousands of lncRNA genes and these genes form a major portion of the genome. This offers exciting possibilities for determination of origins and functions, as well as the elucidation of possible roles in disease.

We have concentrated on a family of long intergenic non-coding RNA (lincRNA) genes that are in the critical 22q11.2 region of human  chromosome 22. The 22q11.2 region is prone to DNA deletions that result in developmental abnormalities. We have determined that several genes from this RNA gene family are specifically formed in low copy repeats (LCR)s that are found in the 22q11.2 region (see figure below). The LCRs are thought to participate in DNA translocations and nonallelic homologous recombinations that lead to 22q11.2 deletions. Although a role for the RNA genes in translocation has not been established, these genes all contain a prominent DNA translocation element and we hypothesize that they may have the potential to participate in DNA translocation. The specificity of these genes also includes expression of the RNA only in a selective tissue, the testes, and this has been established by other labs.  

In addition to lincRNA gene properties at the DNA level, the long term goal of the research is to catalog all the lncRNA genes in the 22q11.2 region and attempt to assess lost RNA transcript functions in a chromosomal 22q11.2 deletion with the aim of determining possible roles in abnormal human embryonic development.  

Chromosomal region 22q11.2. lincRNA genes (#s 1-7) are specifically formed in low copy repeats (LCR)s in the 22q1.2 region and originate from copies of the lincRNA gene FAM230C in LCRs (Delihas, 2018).