RNA Biology Laboratory

Outline

In a classical view of the “central dogma,” genetic information encoded in DNA is transcribed into RNA, and is subsequently translated into protein that finally regulates physiological events in living organisms. During the last decade, however, an extensive amount of work has been done clarifying the role of small non protein-coding (noncoding) RNAs that regulate gene expression through a mechanism collectively called RNA-mediated gene silencing. In addition, recent transcriptome analyses identified a huge number of noncoding RNAs transcribed from the mammalian genome, raising a possibility that these noncoding RNA might provide a basis for the complexity of the higher organism. We are especially interested in a group of noncoding RNAs that stably accumulate in the nucleus, forming particular nuclear structures. These architectural nuclear noncoding RNAs are specific to higher vertebrates, and we are trying to reveal novel nuclear processes regulated by these evolutionarily “new” biomaterials.

Recent Research Topic

Evolutionarily “new” mRNA-like noncoding RNAs

Fig. 1 Expression pattern of Gomafu in E9.5 mouse embryo

Gomafu is specifically expressed in the nervous system.

Fig. 2 Distribution of mRNA-like noncoding RNAs revealed by fluorescent in situ hybridization

RNAs are shown in green and DAPI-stained nuclei are shown in magenta. From left to right: Gomafu in pyramidal neuron in the cerebral cortex of adult mouse, Malat1 and MENε/βin mouse embryonic fibroblasts. Malat1 and MENε/β localizes to the nuclear speckles and paraspeckles, respectively.

During a course of screening for genes that are specifically expressed in a particular subset of neurons, we have identified a novel mRNA-like noncoding RNA, Gomafu. Gomafu is widely expressed in the nervous system throughout the developmental period, and intense expression continues into adult life. The Gomafu gene consists of 7 exons, and its spliced and polyadenylated mature transcripts abundantly accumulate in the nucleus, unlike other protein-coding mRNAs that are immediately transported to the cytoplasm upon removal of their intron sequences. Fluorescent in situ hybridization analysis revealed that Gomafu RNAs form numerous bodies that do not overlap with known nuclear domains such as nucleoli, nuclear speckles, paraspeckles and Cajal bodies. We named this atypical mRNA-like noncoding gene Gomafu after the spotted distribution of its transcripts within the nucleus (“gomafu” means “speckled” in Japanese). Gomafu is biochemically fractionated into the nuclear matrix, which remains after extraction with nonionic detergent and high salt as well as DNaseI treatment. These observations suggest that Gomafu regulates certain molecular processes associated with the nuclear matrix, which might be important for proper functioning of the nervous system. In order to test this hypothesis, we made a mutant mouse that lacks the Gomafu gene. We are in the process of analyzing the phenotypes of these mice, and preliminary data shows that Gomafu regulates the behavior of individual animals. We are also studying the physiological function of anosther nuclear enriched mRNA-like noncoding RNA Malat1 and MENε/β using the reverse genetic approach. These nuclear mRNA-like noncoding RNAs are specifically found in mammalian species, raising the possibility that these evolutionarily “new” noncoding RNAs might enable highly complex nuclear processes specific to the higher organisms.