Circular Intronic Long Noncoding RNAs

Zhang, Yang; Zhang, Xiao‐Ou; Tian, Chen; Xiang, Jianfeng; Yin, Qingrui; Xing, Yu-Hang; Zhu, Shanshan; Yang, Li; Chen, Lingling

doi:10.1016/j.molcel.2013.08.017

Cited by 1,933 publications

(2,044 citation statements)

References 54 publications

Supporting

Mentioning

1,936

Contrasting

Unclassified

Order By: Relevance

“…4D). Cytosine branchpoints have been shown to be resistant to debranching (Hornig et al 1986) and may comprise a distinct subset recently associated with stable lariat and long noncoding RNA formation (Zhang et al 2013).…”

Section: Branchpoint Featuresmentioning

confidence: 99%

Genome-wide discovery of human splicing branchpoints

et al. 2015

View full text Add to dashboard Cite

During the splicing reaction, the 59 intron end is joined to the branchpoint nucleotide, selecting the next exon to incorporate into the mature RNA and forming an intron lariat, which is excised. Despite a critical role in gene splicing, the locations and features of human splicing branchpoints are largely unknown. We use exoribonuclease digestion and targeted RNA-sequencing to enrich for sequences that traverse the lariat junction and, by split and inverted alignment, reveal the branchpoint. We identify 59,359 high-confidence human branchpoints in >10,000 genes, providing a first map of splicing branchpoints in the human genome. Branchpoints are predominantly adenosine, highly conserved, and closely distributed to the 39 splice site. Analysis of human branchpoints reveals numerous novel features, including distinct features of branchpoints for alternatively spliced exons and a family of conserved sequence motifs overlapping branchpoints we term B-boxes, which exhibit maximal nucleotide diversity while maintaining interactions with the keto-rich U2 snRNA. Different B-box motifs exhibit divergent usage in vertebrate lineages and associate with other splicing elements and distinct intron-exon architectures, suggesting integration within a broader regulatory splicing code. Lastly, although branchpoints are refractory to common mutational processes and genetic variation, mutations occurring at branchpoint nucleotides are enriched for disease associations.[Supplemental material is available for this article.]The majority of human genes are spliced, a process whereby introns are removed from the nascent RNA and the remaining exonic sequence joined together into a mature RNA transcript. In addition, alternative splicing generates complex networks of isoforms from human gene loci and plays a major role in shaping the diversity of the transcriptome (Kapranov et al. 2005;Gerstein et al. 2007;Djebali et al. 2012).Splicing occurs in the spliceosome, a large ribonucleoprotein complex that recognizes at least three genetic elements within each intron: the 59 splice site (59SS), the 39 splice site (39SS), and the branchpoint (Will and L€ uhrmann 2011). RNU2-1, the U2 spliceosomal RNA (snRNA) base pairs to the sequence surrounding the unpaired branchpoint nucleotide, which then undergoes transesterification with the 59 end of the intron to form a closed lariat structure. The spliceosome then scans for the downstream 39 splice site, which undergoes a second trans-esterification reaction to join together the two exon ends and excise the intron lariat (Fig.

show abstract

Section: Branchpoint Featuresmentioning

confidence: 99%

Genome-wide discovery of human splicing branchpoints

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Indeed, recent studies have revealed that circRNAs are differentially expressed in different human cell lines and tissues, serve as regulators of transcription and protein expression and can act as miRNA sponges. [4][5][6][7] Several different types of RNA circles originating from diverse cellular processes have been identified. Most eukaryotic circRNAs result from splicing reactions that are catalyzed either by the spliceosome or ribozymes corresponding to Group I and Group II introns.…”

Section: Introductionmentioning

confidence: 99%

High-throughput sequencing reveals circular substrates for an archaeal RNA ligase

et al. 2017

View full text Add to dashboard Cite

It is only recently that the abundant presence of circular RNAs (circRNAs) in all kingdoms of Life, including the hyperthermophilic archaeon Pyrococcus abyssi, has emerged. This led us to investigate the physiologic significance of a previously observed weak intramolecular ligation activity of Pab1020 RNA ligase. Here we demonstrate that this enzyme, despite sharing significant sequence similarity with DNA ligases, is indeed an RNA-specific polynucleotide ligase efficiently acting on physiologically significant substrates. Using a combination of RNA immunoprecipitation assays and RNA-seq, our genome-wide studies revealed 133 individual circRNA loci in P. abyssi. The large majority of these loci interacted with Pab1020 in cells and circularization of selected C/D Box and 5S rRNA transcripts was confirmed biochemically. Altogether these studies revealed that Pab1020 is required for RNA circularization. Our results further suggest the functional speciation of an ancestral NTase domain and/or DNA ligase toward RNA ligase activity and prompt for further characterization of the widespread functions of circular RNAs in prokaryotes. Detailed insight into the cellular substrates of Pab1020 may facilitate the development of new biotechnological applications e.g. in ligation of preadenylated adaptors to RNA molecules.

show abstract

“…The size distributions of the high‐quality reads were varied from 18 to 28 nts in our library and the peak was at the 25 nt , which was on par with previous studies (Ge et al., 2013; Liang, Feng, Zhou, & Gao, 2013; Sattar et al., 2012). Our study indicated the unique read distributes of 26–28 nts with a relative lower abundance, which is common in many small RNA libraries (Chang et al., 2016; Jagadeeswaran et al., 2010; Surridge et al., 2011; Zhang et al., 2013), indicating the presence of piRNAs. Piwi RNAs (piRNAs) are the class of small RNAs mediating chromatin modifications (Ross, Weiner, & Lin, 2014) which are derived mainly from retrotransposons and other repetitive elements with high sequence diversity (Ross et al., 2014; Siomi, Sato, Pezic, & Aravin, 2011; Zhang et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Our study indicated the unique read distributes of 26–28 nts with a relative lower abundance, which is common in many small RNA libraries (Chang et al., 2016; Jagadeeswaran et al., 2010; Surridge et al., 2011; Zhang et al., 2013), indicating the presence of piRNAs. Piwi RNAs (piRNAs) are the class of small RNAs mediating chromatin modifications (Ross, Weiner, & Lin, 2014) which are derived mainly from retrotransposons and other repetitive elements with high sequence diversity (Ross et al., 2014; Siomi, Sato, Pezic, & Aravin, 2011; Zhang et al., 2013). Thus, our results indicated that T. tabaci genome not only harbors miRNAs but also other small RNAs such as piRNAs that might be involved in the transgenerational epigenetic inheritance (Weick & Miska, 2014).…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide identification, expression profiling, and target gene analysis of microRNAs in the Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), vectors of tospoviruses (Bunyaviridae)

Rebijith

Asokan

Hande

et al. 2018

Ecology and Evolution

View full text Add to dashboard Cite

Thrips tabaci Lindeman is an important polyphagous insect pest species estimated to cause losses of more than U.S. $1 billion worldwide annually. Chemical insecticides are of limited use in the management of T. tabaci due to the thigmokinetic behavior and development of resistance to insecticides. There is an urgent need to find alternative management strategies. Small noncoding RNAs (sncRNAs) especially microRNAs (miRNAs) hold great promise as key regulators of gene expression in a wide range of organisms. MiRNAs are a group of endogenously originated sncRNA known to regulate gene expression in animals, plants, and protozoans. In this study, we explored these RNAs in T. tabaci using deep sequencing to provide a basis for future studies of their biological and physiological roles in governing gene expression. Apart from snoRNAs and piRNAs, our study identified nine novel and 130 known miRNAs from T. tabaci. Functional classification of the targets for these miRNAs predicted that majority are involved in regulating transcription, translation, signal transduction and genetic information processing. The higher expression of few miRNAs (such as tta‐miR‐281, tta‐miR‐184, tta‐miR‐3533, tta‐miR‐N1, tta‐miR‐N7, and tta‐miR‐N9) in T. tabaci pupal and adult stages reflected their possible role in larval and adult development, metamorphosis, parthenogenesis, and reproduction. This is the first exploration of the miRNAome in T. tabaci, which not only provides insights into their possible role in insect metamorphosis, growth, and development but also offer an important resource for future pest management strategies.

show abstract

Circular Intronic Long Noncoding RNAs

Cited by 1,933 publications

References 54 publications

Genome-wide discovery of human splicing branchpoints

Genome-wide discovery of human splicing branchpoints

High-throughput sequencing reveals circular substrates for an archaeal RNA ligase

Genome‐wide identification, expression profiling, and target gene analysis of microRNAs in the Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), vectors of tospoviruses (Bunyaviridae)

Contact Info

Product

Resources

About