Identification and Characterization of Novel Genotoxic Stress-Inducible Nuclear Long Noncoding RNAs in Mammalian Cells

Whole transcriptome analyses have revealed a large number of novel transcripts including long and short noncoding RNAs (ncRNAs). Currently, there is great interest in characterizing the functions of the different classes of ncRNAs and their relevance to cellular processes. In particular, nuclear long ncRNAs may be involved in controlling various aspects of biological regulation, such as stress responses. By a combination of bioinformatic and experimental approaches, we identified 25 novel nuclear long ncRNAs from 6,088,565 full-length human cDNA sequences. Some nuclear long ncRNAs were conserved among vertebrates, whereas others were found only among primates. Expression profiling of the nuclear long ncRNAs in human tissues revealed that most were expressed ubiquitously. A subset of the identified nuclear long ncRNAs was induced by the genotoxic agents mitomycin C or doxorubicin, in HeLa Tet-off cells. There were no commonly altered nuclear long ncRNAs between mitomycin C- and doxorubicin-treated cells. These results suggest that distinct sets of nuclear long ncRNAs play roles in cellular defense mechanisms against specific genotoxic agents, and that particular long ncRNAs have the potential to be surrogate indicators of a specific cell stress

Studies on the morphology of the inner ear and semicircular canal endorgan projections of ha, a medaka behavior mutant.

The morphology of the inner ear was investigated in the mutant strain ha of medaka (Oryzias latipes). The ha is a recessive mutant and ha homozygotes are viable but show abnormal circular swimming behavior. In adult ha/ha medaka, more than one semicircular canals are absent. In the most abnormal cases, no canals are present at all and the membranous labyrinth of the inner ear exhibits a simple rugby-ball-like structure. In spite of the apparent absence of the canals, however, receptor endorgans of the canals (crista ampullaris) and the nerves innervating the cristae (ampullar nerves) are present. Otoliths and associated receptor epithelia (maculae) as well as octaval nerve branches innervating maculae are also present, except utricular otoliths that are absent or extremely small if present. Projections of the ampullar nerves were also investigated, because central connections of the nerves may be also abnormal. Tract-tracing studies, however, revealed similar central projection patterns of primary afferents in the mutant and wild-type brains. These results suggest that membranes of prospective semicircular canals fail to form tubular structures and fuse with the membrances of otolith organs in ha/ha medaka. These results also suggest that abnormal morphology of the semicircular canals as well as the utricular otolith underlies the abnormal swimming behavior of the ha/ha medaka, in spite of apparently normal central projections of the ampullar nerves