Discovery of Replicating Circular RNAs by RNA-Seq and Computational Algorithms

Replicating circular RNAs are independent plant pathogens known as viroids, or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs. The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demandi...

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Vydáno v:PLoS pathogens Ročník 10; číslo 12; s. e1004553
Hlavní autoři: Zhang, Zhixiang, Qi, Shuishui, Tang, Nan, Zhang, Xinxin, Chen, Shanshan, Zhu, Pengfei, Ma, Lin, Cheng, Jinping, Xu, Yun, Lu, Meiguang, Wang, Hongqing, Ding, Shou-Wei, Li, Shifang, Wu, Qingfa
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 01.12.2014
Public Library of Science (PLoS)
Témata:
Algorithms
Base Sequence
Biology and Life Sciences
Computational Biology - methods
Deoxyribonucleic acid
DNA
DNA methylation
Flowers & plants
Malus
Molecular Sequence Data
Nucleic Acid Conformation
Phylogeny
RNA - genetics
RNA polymerase
RNA sequencing
RNA, Viral - genetics
Sequence Analysis, RNA - methods
Viroids - genetics
Viroids - physiology
Virus Replication - physiology
Viruses
Vitis
ISSN:1553-7374, 1553-7366, 1553-7374
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Shrnutí:Replicating circular RNAs are independent plant pathogens known as viroids, or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs. The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demanding and time-consuming. We previously described an approach for homology-independent discovery of replicating circular RNAs by analysing the total small RNA populations from samples of diseased tissues with a computational program known as progressive filtering of overlapping small RNAs (PFOR). However, PFOR written in PERL language is extremely slow and is unable to discover those subviral pathogens that do not trigger in vivo accumulation of extensively overlapping small RNAs. Moreover, PFOR is yet to identify a new viroid capable of initiating independent infection. Here we report the development of PFOR2 that adopted parallel programming in the C++ language and was 3 to 8 times faster than PFOR. A new computational program was further developed and incorporated into PFOR2 to allow the identification of circular RNAs by deep sequencing of long RNAs instead of small RNAs. PFOR2 analysis of the small RNA libraries from grapevine and apple plants led to the discovery of Grapevine latent viroid (GLVd) and Apple hammerhead viroid-like RNA (AHVd-like RNA), respectively. GLVd was proposed as a new species in the genus Apscaviroid, because it contained the typical structural elements found in this group of viroids and initiated independent infection in grapevine seedlings. AHVd-like RNA encoded a biologically active hammerhead ribozyme in both polarities, and was not specifically associated with any of the viruses found in apple plants. We propose that these computational algorithms have the potential to discover novel circular RNAs in plants, invertebrates and vertebrates regardless of whether they replicate and/or induce the in vivo accumulation of small RNAs.
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The authors have declared that no competing interests exist.
Conceived and designed the experiments: SL QW ZZ. Performed the experiments: ZZ SQ SC NT XZ JC YX. Analyzed the data: QW PZ LM SWD. Contributed reagents/materials/analysis tools: ML HW QW. Wrote the paper: ZZ QW SL SWD.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004553