Gallo A, Dolfini D, Bernardini A, Gnesutta N, Mantovani R
Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Genomics. 2023 Sep;115(5):110694. doi: 10.1016/j.ygeno.2023.110694. Epub 2023 Aug 1.
NF-YA, the regulatory subunit of the trimeric CCAAT-binding transcription factor NF-Y, is present in vertebrates in two major alternative spliced isoforms: NF-YAl and NF-YAs, differing for the presence of exon-3. NF-YAx, a third isoform without exon-3/-5, was reported only in human neuronal cells and tumors. These events affect the Trans-Activation Domain. We provide here evidence for the expression of NF-YAx and for the existence of a new isoform, NF-YAg, skipping only exon-5. These isoforms are abundant in Aves, but not in reptiles, and are the prevalent transcripts in the initial phases of embryo development in chicken. Finally, we analyzed NF-YAg and NF-YAx amino acid sequence using AlphaFold: absence of exon-5 denotes a global reduction of β-stranded elements, while removal of the disordered exon-3 sequence has limited effects on TAD architecture. These data identify an expanded program of NF-YA isoforms within the TAD in Aves, implying a role during early development.
NF-YA是三聚体CCAAT结合转录因子NF-Y的调节亚基，在脊椎动物中以两种主要的可变剪接异构体形式存在：NF-YAl和NF-YAs，它们因外显子3的存在与否而不同。NF-YAx是第三种没有外显子3/5的异构体，仅在人类神经细胞和肿瘤中被报道。这些事件影响反式激活结构域。我们在此提供了NF-YAx表达的证据以及一种新异构体NF-YAg存在的证据，NF-YAg仅跳过外显子5。这些异构体在鸟类中丰富，但在爬行动物中不存在，并且是鸡胚胎发育初始阶段的主要转录本。最后，我们使用AlphaFold分析了NF-YAg和NF-YAx的氨基酸序列：外显子5的缺失表示β链元件整体减少，而无序外显子3序列的去除对TAD结构的影响有限。这些数据确定了鸟类TAD内NF-YA异构体的扩展程序，暗示其在早期发育中的作用。
