A novel class of small non-coding RNAs

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Central to the flow of genetic information (DNA makes RNA makes protein), small RNA species that do not code for proteins, such as microRNAs, have evolved as key regulators of gene expression; this is required to preserve well-balanced protein expression/levels, to maintain normal cellular functions and, for the organisms, to remain fit and healthy.    Contrary to current scientific (mis?)conception, that no RNA of fewer than 16 nucleotides (nt) can be biologically relevant, we serendipitously discovered a 12-nt long RNA species that could compete with the microRNA regulation of mRNA translation into proteins in human cells.    Analyzing RNA extracted from 12 different primary and cultured cell types, from 5 different species, in the window of RNA sizes comprised between 8 and 30 nt, we identified unusually little RNAs (ulRNAs) of 12 and 13 nt that were often more abundant than 19 to 24-nt microRNAs. Most of the 12-nt RNAs corresponded to a unique sequence, which we have termed dRNA ("d" stands for dozen, douze or duodecim [in Latin]), whereas most 13-nt RNAs consisted of the dRNA sequence with a C at its 5'end (C-dRNA). The dRNA sequence mapped, in the human and mouse genomes, to the 5' end of 5.8S ribosomal RNA, and thus constitute a ribosomal RNA fragment (rRF).    The level of dRNA/C-dRNA was much lower in platelets, which are also known for their very low protein output, suggesting a positive association between dRNA/C-dRNA levels and mRNA translation.    With the overall objective of elucidating the molecular biology, role, function and importance of ulRNAs, this proposal aims to delineate the origin, biogenesis pathway and effector protein complexes involved in the role and function of dRNA/C-dRNA in human and mouse cells.    To confirm our findings and the authenticity of the dRNA/C-dRNA sequences, we will perform additional RNA-Seq analyses and prioritize the validation of an original, sensitive and specific quantitative PCR (qPCR)-based detection method. This qPCR method will also allow us to detect and monitor dRNA/C-dRNA levels under the various experimental settings that will be deployed to characterize this novel class of unusually little RNAs and to elucidate their role, function and importance in human and mouse cells.    Challenging our current scientific beliefs, this research program is expected to confirm the existence of a new class of non-coding RNAs and unveil their role and importance in the increasingly complex mechanisms regulating gene expression in eukaryotes. With this proposal, we hope to establish ulRNAs as a new research area and encourage efforts in this field of RNA biology, in order to improve our understanding of life. Our Institution is closely monitoring our progress and is ready to protect our intellectual property, initially through patenting of our qPCR-based, dRNA/C-dRNA detection method and derived applications, as soon as their function is elucidated.