title: Targeted mRNA degradation by complex-mediated delivery of antisense RNAs to intracellular human mitochondria.
abstract: Mitochondrial dysfunction underlies a large number of acute or progressive diseases, as well as aging. However, proposed therapies for mitochondrial mutations suffer from poor transformation of mitochondria with exogenous DNA, or lack of functionality of the transferred nucleic acid within the organelle. We show that a transfer RNA import complex (RIC) from the parasitic protozoon Leishmania tropica rapidly and efficiently delivered signal-tagged antisense (STAS) RNA or DNA to mitochondria of cultured human cells. STAS-induced specific degradation of the targeted mitochondrial mRNA, with downstream effects on respiration. These results reveal the existence of a novel small RNA-mediated mRNA degradation pathway in mammalian mitochondria, and suggest that RIC-mediated delivery could be used to target therapeutic RNAs to the organelle within intact cells.
authors.affiliation: Genetic Engineering Laboratory, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700032, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Bidesh
authors.initials: B
authors.lastname: Mahata
authors.forename: Biraj
authors.initials: B
authors.lastname: Mahato
authors.forename: Samit
authors.initials: S
authors.lastname: Adhya
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D019069:Cell Respiration; D018390:Gene Targeting; D006801:Humans; D007895:Leishmania tropica / Q000235:genetics; D008928:Mitochondria / Q000235:genetics* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D034443:RNA Transport; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D016053:RNA, Protozoan / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D012365:RNA, Transfer, Tyr / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology
chemical_list: D024101:Mitochondrial Proteins; D016372:RNA, Antisense; D016053:RNA, Protozoan; D012365:RNA, Transfer, Tyr