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1.
Cell Res ; 34(7): 504-521, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38811766

ABSTRACT

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.


Subject(s)
Adenine Nucleotide Translocator 2 , Mitochondria , Mitochondrial Membranes , RNA, Double-Stranded , Animals , Adenine Nucleotide Translocator 2/metabolism , Adenine Nucleotide Translocator 2/genetics , Humans , RNA, Double-Stranded/metabolism , Mitochondria/metabolism , Mitochondrial Membranes/metabolism , Mice , Immunity, Innate , RNA Transport , HEK293 Cells , Mice, Inbred C57BL
2.
Protein Cell ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38721690

ABSTRACT

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

3.
J Opt Soc Am A Opt Image Sci Vis ; 39(4): 594-599, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35471382

ABSTRACT

A simple monolayer graphene metamaterial based on silicon/silica substrates is proposed, and typical triple-plasmon-induced transparency (PIT) is realized in the terahertz band. The physical mechanism is analyzed by coupled mode theory (CMT), and the results of CMT agree well with the finite-difference time-domain simulation. A multimode electro-optical switch can be designed by dynamic tuning, and the modulation degrees of its resonant frequencies are 84.0%, 87.3%, 83.0%, 88.1%, and 76.7%. In addition, triple-PIT gradually degenerates into dual-PIT with a decrease in the length of one bright mode. Interestingly, the group index can reach 770 at Ef=0.8eV, which shows that it can be designed as a slow light device with extraordinary ability. Therefore, the results of this paper are of great significance to the research and design of electro-optical switches and slow light devices in the terahertz band.

4.
J Opt Soc Am A Opt Image Sci Vis ; 39(3): 377-382, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35297420

ABSTRACT

A terahertz-band metamaterial composed of multilayer patterned graphene is proposed and triple plasmon-induced transparency is excited by coupling three bright modes with one dark mode. The Lorentz curve calculated by the coupled-mode theory agrees well with the finite-difference time-domain results. Dynamic tuning is investigated by changing the Fermi level. Multimode electro-optics switching can be designed and achieved, and the amplitude modulations of four resonance frequencies are 94.3%, 92.8%, 90.7%, and 93%, respectively, which can realize the design of synchronous and asynchronous electro-optics switches. It is hoped that these results can provide theoretical support and guidance for the future design and application of photonic and optoelectronic devices.

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