The divergence rate between the alignable genomes of humans and chimpanzees is as little as 1.23%.Their phenotypical difference was hypothesized to be accounted for by gene regulation.We construct the cis-regulatory e...The divergence rate between the alignable genomes of humans and chimpanzees is as little as 1.23%.Their phenotypical difference was hypothesized to be accounted for by gene regulation.We construct the cis-regulatory element frequency(CREF)matrix to represent the proximal regulatory sequences for each species.Each CREF matrix is further decomposed into dual eigen-modules.By comparing the CREF modules of four existing hominid species,we examine their quantitative and qualitative changes along evolution.We identified two saltations:one between the 4th and 5th,the other between the 9th and 10th eigen-levels.The cognition and intelligence unique to humans are thus found from the saltations at the molecular level.They include long-term memory,cochlea/inner ear morphogenesis that enables the development of human language/music,social behavior that allows us to live together peacefully and to work collaboratively,and visual/observational/associative learning.Moreover,we found exploratory behavior crucial for humans’creativity,the GABA-B receptor activation that protects our neurons,and serotonin biosynthesis/signaling that regulates our happiness.We observed a remarkable increase in the number of motifs present on Alu elements on the 4th/9th motifeigenvectors.The cognition and intelligence unique to humans can,by and large,be identified using only the CREF profiles without any a priori.Although gradual evolution might be the only mode in the mutations of protein sequences,the evolution of gene regulation has both gradual and saltational modes,which could be explained by the framework of CREF eigen-modules.展开更多
Background： Circular RNAs （circRNAs） from back-spliced exon（s） are characterized by the covalently closed loop feature with neither 5＇ to 3＇ polarity nor polyadenylated tail. By using specific computational app...Background： Circular RNAs （circRNAs） from back-spliced exon（s） are characterized by the covalently closed loop feature with neither 5＇ to 3＇ polarity nor polyadenylated tail. By using specific computational approaches that identify reads mapped to back-splice junctions with a reversed genomic orientation, ten thousands of cireRNAs have been recently re-identified in various cell lines/tissues and across different species. Increasing lines of evidence suggest that back-splicing is catalyzed by the canonical spliceosomal machinery and modulated by cis-elements and trans-factors. Results： In this mini-review, we discuss our current understanding of circRNA biogenesis regulation, mainly focusing on the complex regulation of complementary sequences, especially Alus in human, on circRNA formation. Conclusions： Back-splicing can be significantly facilitated by RNA pair formed by orientation-opposite complementary sequences that juxtapose flanking introns of circularized exon（s）. RNA pair formed within individual introns competes with RNA pair formed across flanking introns in the same gene locus, leading to distinct choices for either canonical splicing or back-splicing. Multiple RNA pairs that bracket different circle-forming exons compete for alternative back-splicing selection, resulting in multiple circRNAs generated in a single gene locus.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:32170679,11871462National Key Research and Development Program of China,Grant/Award Number:2022YFA1004801+2 种基金Chinese Academy of Sciences,the Strategic Priority Research Program,Grant/Award Number:XDB13040600National Center for Mathematics and Interdisciplinary Sciences,Chinese Academy of SciencesKey Laboratory of Systems and Control,Chinese Academy of Sciences。
文摘The divergence rate between the alignable genomes of humans and chimpanzees is as little as 1.23%.Their phenotypical difference was hypothesized to be accounted for by gene regulation.We construct the cis-regulatory element frequency(CREF)matrix to represent the proximal regulatory sequences for each species.Each CREF matrix is further decomposed into dual eigen-modules.By comparing the CREF modules of four existing hominid species,we examine their quantitative and qualitative changes along evolution.We identified two saltations:one between the 4th and 5th,the other between the 9th and 10th eigen-levels.The cognition and intelligence unique to humans are thus found from the saltations at the molecular level.They include long-term memory,cochlea/inner ear morphogenesis that enables the development of human language/music,social behavior that allows us to live together peacefully and to work collaboratively,and visual/observational/associative learning.Moreover,we found exploratory behavior crucial for humans’creativity,the GABA-B receptor activation that protects our neurons,and serotonin biosynthesis/signaling that regulates our happiness.We observed a remarkable increase in the number of motifs present on Alu elements on the 4th/9th motifeigenvectors.The cognition and intelligence unique to humans can,by and large,be identified using only the CREF profiles without any a priori.Although gradual evolution might be the only mode in the mutations of protein sequences,the evolution of gene regulation has both gradual and saltational modes,which could be explained by the framework of CREF eigen-modules.
文摘Background： Circular RNAs （circRNAs） from back-spliced exon（s） are characterized by the covalently closed loop feature with neither 5＇ to 3＇ polarity nor polyadenylated tail. By using specific computational approaches that identify reads mapped to back-splice junctions with a reversed genomic orientation, ten thousands of cireRNAs have been recently re-identified in various cell lines/tissues and across different species. Increasing lines of evidence suggest that back-splicing is catalyzed by the canonical spliceosomal machinery and modulated by cis-elements and trans-factors. Results： In this mini-review, we discuss our current understanding of circRNA biogenesis regulation, mainly focusing on the complex regulation of complementary sequences, especially Alus in human, on circRNA formation. Conclusions： Back-splicing can be significantly facilitated by RNA pair formed by orientation-opposite complementary sequences that juxtapose flanking introns of circularized exon（s）. RNA pair formed within individual introns competes with RNA pair formed across flanking introns in the same gene locus, leading to distinct choices for either canonical splicing or back-splicing. Multiple RNA pairs that bracket different circle-forming exons compete for alternative back-splicing selection, resulting in multiple circRNAs generated in a single gene locus.
