Regulatory RNAs and the design of cancer therapy using RNA biotechnology

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It has recently been revealed that non-coding RNAs (regulatory RNAs) play important roles in the regulation of gene expression. The aims of this study were to manifest the role of microRNAs in hematopoietic differentiation and leukemogenesis, to clarify the regulation of telomerase activity, and to develop new methods for cancer diagnosis and therapy using RNA biotechnology on the basis of the physiological functions of regulatory RNAs. The following results were obtained: i) Knockdown of the leukemia fusion gene by siRNAs resulted in down-regulation of self-renewal activity and induction of differentiation, suggesting that these siRNAs can be used as therapeutics for leukemia; ii) MicroRNA expressions changed dynamically during differentiation to monocyte/macrophage in HL-60 cells; iii) RNA aptamers against the KRAS oncoprotein and other cancer-related proteins were obtained, which will become seeds for new methods of cancer diagnosis and therapy; iv) Telomerase is a specialized reverse transcriptase that synthesizes telomeric DNA using an intrinsic RNA template. Although the genes encoding the catalytic subunit and the template RNA have been identified, little is known about how telomerase is recruited to telomeres in vivo. In this study, we tried to biochemically identify such factors in human and fission yeast. We found that human telomerase is very resistant to extraction. However, we isolated fission yeast proteins Poz1 and Ccq1 that negatively and positively regulate telomerase.