Gene knockdown approaches using antisense oligo nucleotides or analogs such as siRNAs and morpholinos have been widely adopted to study gene functions although the off-target issue has been always a concern in these s...Gene knockdown approaches using antisense oligo nucleotides or analogs such as siRNAs and morpholinos have been widely adopted to study gene functions although the off-target issue has been always a concern in these studies.On the other hand,classic genetic analysis relies on the availability of loss-offunction or gain-of-function mutants.The fast development of genome editing technologies such as TALEN and CRISPR/Cas9 has greatly facilitated the generation of null mutants for the functional studies of target genes in a variety of organisms such as zebrafish.Surprisingly,an unexpected discrepancy was observed between morphant phenotype and mutant phenotype for many genes in zebrafish,i.e.,while the morphant often displays an obvious phenotype,the corresponding null mutant appears relatively normal or only exhibits a mild phenotype due to gene compensation.Two recent reports have partially answered this intriguing question by showing that a pre-mature termination codon and homologous sequence are required to elicit the gene compensation and the histone modifying complex COMPASS is involved in activating the expression of the compensatory genes.Here,I summarize these exciting new progress and try to redefine the concept of genetic compensation and gene compensation.展开更多
基金supported by National Key R&D Program of China (2018YFA0800501)National Natural Science Foundation of China (Nos.31571495, 31830113 and 31330050)
文摘Gene knockdown approaches using antisense oligo nucleotides or analogs such as siRNAs and morpholinos have been widely adopted to study gene functions although the off-target issue has been always a concern in these studies.On the other hand,classic genetic analysis relies on the availability of loss-offunction or gain-of-function mutants.The fast development of genome editing technologies such as TALEN and CRISPR/Cas9 has greatly facilitated the generation of null mutants for the functional studies of target genes in a variety of organisms such as zebrafish.Surprisingly,an unexpected discrepancy was observed between morphant phenotype and mutant phenotype for many genes in zebrafish,i.e.,while the morphant often displays an obvious phenotype,the corresponding null mutant appears relatively normal or only exhibits a mild phenotype due to gene compensation.Two recent reports have partially answered this intriguing question by showing that a pre-mature termination codon and homologous sequence are required to elicit the gene compensation and the histone modifying complex COMPASS is involved in activating the expression of the compensatory genes.Here,I summarize these exciting new progress and try to redefine the concept of genetic compensation and gene compensation.
