Probes for LONG

Non-coding RNAs (ncRNAs) play a critical role in the entire body, and their mis-regulation is often associated with disease. In parallel with the advances in high-throughput sequencing technologies, there is a great deal of focus on this broad class of RNAs. Although these molecules are not translated into proteins, they are now well established as significant regulatory components in many biological pathways and pathological conditions. ncRNAs can be roughly divided into two main sub-groups based on the length of the transcript, with both the small and long non-coding RNAs having diverse regulatory functions. The smaller length group includes ribosomal RNAs (rRNA), transfer RNAs (tRNA), small nuclear RNAs (snRNA), small nucleolar RNAs (snoRNA), microRNAs (miRNA), small interfering RNAs (siRNA), and PIWI-associated RNAs (piRNA). The longer length group includes linear long non-coding RNAs (lncRNA) and circular RNAs (circRNA). This review is designed to present the different classes of small and long ncRNA molecules and describe some of their known roles in physiological and pathological conditions, as well as methods used to assess the validity and function of miRNAs and lncRNAs, with a focus on their role and functions in the inner ear, hearing and deafness.

The Small Nucleolar Host Gene 14 (SNHG14) is a host gene for small non-coding RNAs, including the SNORD116 small nucleolar C/D box RNA encoding locus. Large deletions of the SNHG14 locus, as well as microdeletions of the SNORD116 locus, lead to the neurodevelopmental genetic disorder Prader-Willi syndrome. This review will focus on the SNHG14 gene, its expression patterns, its role in human cancer, and the possibility that single nucleotide variants within the locus contribute to human phenotypes in the general population. This review will also include new in silico data analyses of the SNHG14 locus and new in situ RNA expression patterns of the Snhg14 RNA in mouse midbrain and hindbrain regions.

Stable intronic sequence RNAs (sisRNAs) are stable, long noncoding RNAs containing intronic sequences. While sisRNAs have been found across diverse species, their level of conservation remains poorly understood. Here we report that the biogenesis and functions of a sisRNA transcribed from the highly conserved Arglu1 locus are distinct in human and Drosophila melanogaster. The Arglu1 genes in both species show similar exon-intron structures where the intron 2 is orthologous and positionally conserved. In humans, Arglu1 sisRNA retains the entire intron 2 and promotes host gene splicing. Mechanistically, Arglu1 sisRNA represses the splicing-inhibitory activity of ARGLU1 protein by binding to ARGLU1 protein and promoting its localization to nuclear speckles, away from the Arglu1 gene locus. In contrast, Drosophila dArglu1 sisRNA forms via premature cleavage of intron 2 and represses host gene splicing. This repression occurs through a local accumulation of dARGLU1 protein and inhibition of telescripting by U1 snRNPs at the dArglu1 locus. We propose that distinct biogenesis of positionally conserved Arglu1 sisRNAs in both species may have led to functional divergence.

Somatosensory neurons are highly heterogeneous with distinct types of neural cells responding to specific stimuli. However, the distribution and roles of cell-type-specific long intergenic noncoding RNAs (lincRNAs) in somatosensory neurons remain largely unexplored. Here, by utilizing droplet-based single-cell RNA-seq (scRNA-seq) and full-length Smart-seq2, we show that lincRNAs, but not coding mRNAs, are enriched in specific types of mouse somatosensory neurons. Profiling of lincRNAs from single neurons located in dorsal root ganglia (DRG) identifies 200 lincRNAs localized in specific types or subtypes of somatosensory neurons. Among them, the conserved cell-type-specific lincRNA CLAP associates with pruritus and is abundantly expressed in somatostatin (SST)-positive neurons. CLAP knockdown reduces histamine-induced Ca2+ influx in cultured SST-positive neurons and in vivo reduces histamine-induced scratching in mice. In vivo knockdown of CLAP also decreases the expression of neuron-type-specific and itch-related genes in somatosensory neurons, and this partially depends on the RNA binding protein MSI2. Our data reveal a cell-type-specific landscape of lincRNAs and a function for CLAP in somatosensory neurons in sensory transmission.