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Igor Ulitsky

Publications and source records attributed to Igor Ulitsky.

3 recordsLinked to original sources

Identification and characterization of key long non-coding RNAs in the auditory system

The auditory system is a complex sensory network with an orchestrated multilayer regulatory program governing its development and maintenance. Accumulating evidence has implicated long non-coding RNAs (lncRNAs) as important regulators in numerous systems, as well as in pathological pathways. However, their function in the auditory system has yet to be explored. Using a set of specific criteria, we selected four lncRNAs expressed in the mouse cochlea, which are conserved in the human transcriptome and are relevant for inner ear function. Bioinformatic characterization demonstrated a lack of coding potential and an absence of evolutionary conservation that represent properties commonly shared by their class members. RNAscope analysis of the spatial and temporal expression profiles revealed specific localization to inner ear cells. Sub-cellular localization analysis presented a distinct pattern for each lncRNA and mouse tissue expression evaluation displayed a large variability in terms of level and location. Our findings establish the expression of specific lncRNAs in different cell types of the auditory system and present a potential pathway by which the lncRNA Gas5 acts in the inner ear. Studying lncRNAs and deciphering their functions may deepen our knowledge of inner ear physiology and morphology and may reveal the basis of as yet unresolved genetic hearing loss-related pathologies. Moreover, our experimental design may be employed as a reference for studying other inner ear-related lncRNAs, as well as lncRNAs expressed in other sensory systems.

genomics↗

A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells

Thousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionary conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD - an abundant and highly conserved cytoplasmic lncRNA. Most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two Pumilio homologs in mammals. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA binding proteins, an activity which positions them at key junctions of cellular signaling pathways.

Molecular Biology↗

Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs

Long noncoding RNAs (lncRNAs) are a diverse class of RNAs with increasingly appreciated functions in vertebrates, yet much of their biology remains poorly understood. In particular, it is unclear to what extent the current catalog of over 10,000 distinct annotated lncRNAs is indeed devoid of genes coding for proteins. Here we review the available computational and experimental schemes for distinguishing between coding and noncoding transcripts and assess the conclusions from their recent genome-wide applications. We conclude that the model most consistent with available data is that a large number of mammalian lncRNAs undergo translation, but only a very small minority of such translation events result in stable and functional peptides. The outcome of the majority of the translation events and their potential biological purposes remain an intriguing topic for future investigation.

Molecular Biology↗