Rigoutsos Research

Miranda, K., T. Huynh, Y. Tay, Y.-S. Ang, W.-L. Tam, A. Thomson, B. Lim and I. Rigoutsos, “A pattern-based method for the identification of microRNA target sites and their corresponding heteroduplexes.” Cell, 126(6):1203-1217, September 2006. doi: 10.1016/j.cell.2006.07.031. PubMed PMID:16990141 .

This paper described one of the first tools for predicting microRNA targets across the entire length of a messenger RNA. The paper demonstrated that a single microRNA can have thousands of targets, as well as showed numerous functioning heteroduplexes where the microRNA seed region contained gaps and/or G:U wobbles. Also, it correctly presaged the existence of microRNA targets in amino acid coding regions and 5´UTRs, and the existence of tens of thousands of human microRNAs.

Tay Y., A. Thomson, T. Huynh, J. Zhang, B. Lim and I. Rigoutsos, “MicroRNAs to Nanog, Oct4 & Sox2 coding regions modulate embryonic stem cell differentiation.” Nature, 455(7216):1124-8, October 2008. doi: 10.1038/nature07299. PubMed PMID:18806776 .

This paper presented one of the first experimental demonstrations that microRNAs can target messenger RNAs within their amino-acid coding regions to drive important processes such as stem cell differentiation. Moreover, it showed that microRNA target sites can be organism-specific and need not be conserved across evolution.

Telonis A.G., R. Magee, P/ Loher, I. Chervoneva, E. Londin, and I. Rigoutsos, “Knowledge about the presence or absence of miRNA isoforms (isomiRs) can successfully discriminate amongst 32 TCGA cancer types.”  Nucleic Acids Res, 45(6):2973-2985, April 2017. doi: https://academic.oup.com/nar/article/45/6/2973/2999732 
PubMed PMID:28206648 PubMed Central PMC5389567.

This paper demonstrated that the identities and abundances of microRNA isoforms that are produced from a single microRNA arm depend on tissue type and disease type. The paper set the stage for the development of isomiR-based biomarkers.

Rigoutsos, I., S.K. Lee, S.Y. Nam, S. Anfossi, B. Pasculli, M. Pichler, Y. Jing, C. Rodriguez-Aguayo, A.G. Telonis, S. Rossi, C. Ivan, T.C. Ivkovic, L. Fabris, P. Clark, H. Ling, M. Shimizu, R.S. Redis, M.Y. Shah, X. Zhang, Y. Okugawa, E.J. Jung, A. Tsirigos, L. Huang, J. Ferdin, R. Gafà, R. Spizzo, M.S. Nicoloso, A.N. Paranjape, M. Shariati, A. Tiron, J.J. Yeh, R. Teruel-Montoya, L. Xiao, S.A. Melo, D. Menter, Z.C. Jiang, E.R. Flores, M. Negrini, A. Goel, M. Bar-Eli, S.A. Mani, C.G. Liu, G. Lopez-Berestein, I. Berindan-Neagoe, M. Esteller, S. Kopetz, G. Lanza, and G.A. Calin, “N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration.” Genome Biology, 18(1):98, May 2017. doi: 10.1186/s13059-017-1224-0. PubMed PMID:28535802 PubMed Central PMC5442648.

This paper shows that dysregulation of a primate-specific long non-coding RNAs can instigate aggressive cancer biology by interfering with endogenous microRNA targeting. Specifically, we showed that the non-coding RNA dubbed N-BLR facilitates the EMT and affects overall patient survival by serving as a decoy target for two endogenous microRNAs.

Telonis A.G. and I. Rigoutsos, “Race disparities in the contribution of miRNA isoforms and tRNA-derived fragments to triple-negative breast cancer.” Cancer Res. doi: 10.1158/0008-5472.CAN-17-1947. PubMed PMID:29229607 PubMed Central PMC5935570.

This paper showed that the interplay of microRNA isoforms and tRNA-derived fragments, and the resulting regulatory control they exert on messenger RNAs, differs between White and African-American patients with in triple negative breast cancer.  It also uncovered race/ethnicity-specific RNA expression differences that might help explain the observed disparities in incidence and disease progression.

Telonis A.G., P. Loher, R. Magee, V. Pliatsika, E. Londin, Y. Kirino, and I. Rigoutsos.  "tRNA Fragments Show Intertwining with mRNAs of Specific Repeat Content and Have Links to Disparities." Cancer Res. 2019 Jun 15;79(12):3034-3049. doi: 10.1158/0008-5472.CAN-19-0789. PubMed PMID:30996049.

This paper presented the first systems-level analysis of tRNA-derived fragments in 32 different cancer types. It showed that fragments from both nuclear and mitochondrial tRNAs are linked to messenger RNAs that belong to concrete pathways, encode proteins with specific subcellular destinations, and have biases in length and in repetitive content.  The paper also linked mitochondrial tRNA-derived fragments to retrograde signaling and genomic architecture and demonstrated the importance of repetitive elements for all analyzed cancers.