Efficient turnover of unnecessary and misfolded RNAs is critical for maintaining the integrity and function of the mitochondria. The mitochondrial RNA degradosome of budding yeast (mtEXO) has been recently studied and characterized; yet no RNA degradation machinery has been identified in the mammalian mitochondria. In this communication, we demonstrated that purified human SUV3 (suppressor of Var1 3) dimer and polynucleotide phosphorylase (PNPase) trimer form a 330-kDa heteropentamer that is capable of efficiently degrading doublestranded RNA (dsRNA) substrates in the presence of ATP, a task the individual components cannot perform separately. The configuration of this complex is similar to that of the core complex of the E. coli RNA degradosome lacking RNase E but very different from that of the yeast mtEXO. The hSUV3-hPNPase complex prefers substrates containing a 3 overhang and degrades the RNA in a 3-to-5 directionality. Deleting a short stretch of amino acids (positions 510 -514) compromises the ability of hSUV3 to form a stable complex with hPNPase to degrade dsRNA substrates but does not affect its helicase activity. Furthermore, two additional hSUV3 mutants with abolished helicase activity because of disrupted ATPase or RNA binding activities were able to bind hPNPase. However, the resulting complexes failed to degrade dsRNA, suggesting that an intact helicase activity is essential for the complex to serve as an effective RNA degradosome. Taken together, these results strongly suggest that the complex of hSUV3-hPNPase is an integral entity for efficient degradation of structured RNA and may be the long sought RNA-degrading complex in the mammalian mitochondria.The current opinion on mitochondrial RNA degradation is largely based on our understanding of the Escherichia coli RNA degradosome and the yeast mitochondrial degradosome (mtEXO). The E. coli RNA degradosome consists of four components: RNase E, an endoribonuclease in which the C terminus serves as the scaffold of the multiprotein complex; PNPase, 4 an ambivalent enzyme that catalyzes 3Ј-to-5Ј phosphorolysis as well as 5Ј-to-3Ј polymerization of RNA; RhlB, a DEAD-box helicase; and enolase, a glycolytic enzyme (1-7). The 4-MDa multi-enzyme complex has been postulated to have a molar ratio of 4 RNase E:12 PNPase:4 RhlB:8 enolase (2, 4, 5, 8 -10). More recently, it has been reported that in the absence of RNase E, RhlB and PNPase can form a 380-kDa complex (2 RhlB:3 PNPase) to degrade dsRNA substrates (11-13). In budding yeast, an ATP-dependent DExH/D-box RNA helicase, Suv3p, and a 3Ј-to-5Ј directed exoribonuclease, Dss1, have been demonstrated to be the essential components of the mtEXO (14). In vitro, the two proteins have been shown to form a heterodimer that is capable of degrading dsRNA substrates containing a 3Ј overhang (15). Unlike its counterpart in the E. coli RNA degradosome, Dss1 does not form a trimeric ring structure but belongs to the RNR family of exoribonucleases that are mainly involved in rRNA maturation in the chloroplast of higher...
Background: Helicase SUV3, polynucleotide phosphorylase (PNPase), or mitochondrial poly(A) polymerases (mtPAP) have individual activity in regulating mitochondrial mRNA (mt-mRNA)-polyadenylated (poly(A)) tails. Results: SUV3 bridges PNPase and mtPAP to form a transient complex in modulating mt-mRNA poly(A) tail length depending on the mitochondrial matrix P i level. Conclusion: mt-mRNA poly(A) tail length is modulated by a SUV3⅐PNPase⅐mtPAP complex. Significance: Mitochondrial energy status affects mt-mRNA poly(A) tail length.
Background: SUV3 helicase is an essential component of mitochondrial degradosome. Results: Using specific genetic mutants, SUV3 was demonstrated to participate in mtDNA replication, which requires ATPase activity and the C-terminal conserved region. Conclusion: SUV3 plays two distinctive roles in maintaining mtDNA stability and RNA turnover. Significance: This study suggests a direct role of SUV3 in maintaining mtDNA stability, paving a foundation for biochemical investigation.
ZBRK1, a zinc finger protein that interacts with breast cancer 1 (BRCA1) and KRAB-ZFP-associated protein 1 (KAP1), has been suggested to serve as a tumor suppressor via repression of tumor metastasis/invasion. To date, the detailed molecular mechanisms for how BRCA1 and KAP1 participate in ZBRK1-mediated transcriptional repression, metastasis and invasion as well as the associated clinical relevance remain unclear. In this study, we demonstrated that both the N- and C-terminal domains of ZBRK1 are important for inhibiting cell proliferation and anchorage-independent growth in cervical cancer. Specifically, the N-terminal KRAB domain of ZBRK1 displayed a more crucial role in inhibiting metastasis and invasion through modulation of KAP1 function in a transcriptionally dependent manner. The loss of ZBRK1 results in an increase of KAP1 expression, which enhanced migration and invasion of cervical cancer cells both the in vitro and in vivo. Moreover, an inverse correlation of expression levels was observed between ZBRK1 and KAP1 following tumor progression from in situ carcinoma to invasive/metastatic cervical cancer specimens. Taken together, the current results indicate that a loss of ZBRK1 contributes to the increased expression of KAP1, potentiating its role to enhance metastasis and invasion. Citation Format: Wei-Jan Wang, Li-Fang Lin, Chien-Feng Li, Wen-Ming Yang, Dennis Ding-Hwa Wang, Wen-Chang Chang, Wen-Hwa Lee, Ju-Ming Wang, Ju-Ming Wang. Loss of ZBRK1 contributes to the increase of KAP1 and promotes KAP1-mediated metastasis and invasion in cervical cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4926. doi:10.1158/1538-7445.AM2013-4926
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.