Abstract
RNA polyadenylation serves a purpose in bacteria and organelles opposite from the role it plays in nuclear systems. The majority of nucleus-encoded transcripts are characterized by stable poly(A) tails at their mature 3′ ends, which are essential for stabilization and translation initiation. In contrast, in bacteria, chloroplasts, and plant mitochondria, polyadenylation is a transient feature which promotes RNA degradation. Surprisingly, in spite of their prokaryotic origin, human mitochondrial transcripts possess stable 3′-end poly(A) tails, akin to nucleus-encoded mRNAs. Here we asked whether human mitochondria retain truncated and transiently polyadenylated transcripts in addition to stable 3′-end poly(A) tails, which would be consistent with the preservation of the largely ubiquitous polyadenylation-dependent RNA degradation mechanisms of bacteria and organelles. To this end, using both molecular and bioinformatic methods, we sought and revealed numerous examples of such molecules, dispersed throughout the mitochondrial genome. The broad distribution but low abundance of these polyadenylated truncated transcripts strongly suggests that polyadenylation-dependent RNA degradation occurs in human mitochondria. The coexistence of this system with stable 3′-end polyadenylation, despite their seemingly opposite effects, is so far unprecedented in bacteria and other organelles.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://mcb.asm.org/.
ACKNOWLEDGMENTS
We thank Ilan Ifergan, Asaf Shafran, Yehuda G. Assraf, Ifat Sher, Simona Zisman, and Dina Ron for the cancer cells and primary fibroblasts; Shiri Solsky and Shachar Uliel for excellent technical assistance; and Victoria Portnoy for the archaeal RNA. We thank members of our laboratory and Robert Lightowlers for critical reading of the manuscript and Jan Piwowarski for the idea of searching the human EST database. Special thanks go to David Stern for critically reading and editing the manuscript.
This work was supported by grants from the Israel Science Foundation (ISF) to G.S. and D.G. and from the Binational Science Foundation (BSF) and Binational Agriculture Science and Development Foundation (BARD) to G.S.