ADAR2為一種ADARs (Adenosine deaminase that acts on RNAs) 酵素，可以催化RNA進行A-to-I (adenosine to inosine) editing的後轉錄修飾，增加基因組的複雜度。我們以生物資訊方法搜尋發現斑馬魚基因組具有兩個ADAR2相似基因，遂將新發現之ADAR2基因命名為ADAR2β，並由RT-PCR結果確定成年斑馬魚腦中會表現ADAR2β。此外，增加斑馬魚ADAR2β表現可增加ADAR2α pre-mRNA之intron 1中某特定位點編輯 (RNA editing)。 為了比較ADAR2α與ADAR2β之生理功能差異，我們針對ADAR2α、ADAR2β設計反義寡核苷酸 (morpholinos) 抑制基因活性。 觀察ADAR2α morphant在表現型、細胞凋亡以及側腺染色實驗發現其發育明顯出現異常；但降低ADAR2β活性結果卻與野生種斑馬魚相同，與抑制ADAR2α所導致斑馬魚早期神經發育異常大相逕庭，表示ADAR2β與ADAR2α在斑馬魚胚體發育中所扮演的生理功能角色有所差異。 此外由於GluR-2 (AMPA receptor subunit) Q/R site為ADAR2影響生理功能的重要受質，故本篇論文亦利用morpholino抑制gria2α (哺乳類之GluR-2 homologue) Q/R editing，結果發現抑制ADAR2α活性或調控gria2α Q/R editing出現問題皆會導致胚體神經發育異常。 本篇論文顯示ADAR2β為ADAR2α的複製基因，可藉由RNA editing編輯彼此的pre-mRNA，且扮演不同的生理功能。ADAR2β已知具有RNA editing功能，但其他生理功能仍有待進一步探討。

ADAR2 is a member of the ADARs (Adenosine deaminase that acts on RNAs) protein family. ADAR2 can post-transcriptionally edit specific adenosine at double-stranded RNA region into inosine (A-to-I RNA editing), and increase the complexity of transcriptome. Two paralogues of ADAR2 have been discovered in the pufferfish (Takifugu rubripes). Using bioinformatic tools, a gene ADAR2β whose sequence is conserved to ADAR2α was found on the 9th chromosome of zebrafish. The RT-PCR analysis showed that ADAR2β was expressed in adult zebrafish brain. In addition, overexpression of ADAR2β (ADAR2β cRNA microinjection into one-cell zygote) can increase the RNA editing level of ADAR2α pre-mRNA. In order to examine the physiological functions of ADAR2α and ADAR2β, we employed antisense morpholinos targeted to ADAR2α and ADAR2β to reduce the expression of these genes. The phenotypes, distribution of apoptotic cells and posterior lateral line neuromasts of mophants indicated that the phenotype of ADAR2β morphant was the same as that of the wild type but different from that of ADAR2α morphant. These results suggested that the physiological functions of ADAR2α and ADAR2β differed. Genetic studies have indicated that the Q/R site of mouse GluR2 (AMPA receptor subunit) is the most important physiological substrate of ADAR2. Therefore, we also made use of a morpholino to suppress the Q/R editing of gira2α□(homologue of mammalian GluR2) to observe if Q/R site of zebrafish gria2α□is also the key site edited by ADAR2. The results showed that both ADAR2α and gria2α Q/R morphants led to abnormal neural development. In this study, we have demonstrated that ADAR2β is the duplicated gene of ADAR2α, and ADAR2α and ADAR2β can mutually modify the pre-mRNA sequences of each other. In addition, the physiological function of ADAR2α is different from that of ADAR2β. ADAR2β possesses RNA editing activity; however, its physiological function remains to be elucidated.

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