Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, USA.
Wiley Interdiscip Rev RNA. 2011 Jan-Feb;2(1):92-105. doi: 10.1002/wrna.36.
The immunoglobulin heavy chain (IgH) genes, which encode one of the two chains of antibody molecules, were the first cellular genes shown to undergo developmentally regulated alternative RNA processing. These genes produce two different mRNAs from a single primary transcript. One mRNA is cleaved and polyadenylated at an upstream poly(A) signal while the other mRNA removes this poly(A) signal by RNA splicing and is cleaved and polyadenylated at a downstream poly(A) site. A broad range of studies have been performed to understand the mechanism of IgH RNA processing regulation during B lymphocyte development. The model that has emerged is much more complex than envisioned by the earliest view of regulation through poly(A) signal choice. Regulation requires that the IgH gene contain competing splice and cleavage-polyadenylation reactions with balanced efficiencies. Because non-IgH genes with these structural features also can be regulated, IgH gene-specific sequence elements are not required for regulation. Changes in cleavage-polyadenylation and RNA splicing, as well as pol II elongation, all contribute to IgH developmental RNA processing regulation. Multiple factors are likely involved in the regulation during B lymphocyte maturation. Additional biologically relevant factors that contribute to IgH regulation remain to be identified and incorporated into a mechanistic model for regulation. Much of the work to date confirms the complex nature of IgH mRNA regulation and suggests that a thorough understanding of this control will remain a challenge. However, it is also likely that such understanding will help elucidate novel mechanisms of RNA processing regulation.
免疫球蛋白重链 (IgH) 基因，编码抗体分子的两条链之一，是第一个被证明经历发育调控的替代 RNA 加工的细胞基因。这些基因从单个初级转录本中产生两种不同的 mRNA。一种 mRNA 在上游 poly(A) 信号处被切割和聚腺苷酸化，而另一种 mRNA 通过 RNA 剪接去除该 poly(A) 信号，并在下游 poly(A) 位点被切割和聚腺苷酸化。已经进行了广泛的研究来了解 B 淋巴细胞发育过程中 IgH RNA 加工调控的机制。出现的模型比通过 poly(A) 信号选择进行调控的最早观点所设想的要复杂得多。调控需要 IgH 基因包含具有平衡效率的竞争剪接和切割聚腺苷酸化反应。由于具有这些结构特征的非 IgH 基因也可以被调控，因此不需要 IgH 基因特异性序列元件来进行调控。切割聚腺苷酸化和 RNA 剪接的变化，以及 pol II 延伸，都有助于 IgH 发育性 RNA 加工调控。在 B 淋巴细胞成熟过程中，可能涉及多种因素的调控。还有许多其他与生物学相关的因素可能参与了调控，有待进一步确定并整合到调控的机制模型中。迄今为止的大部分工作证实了 IgH mRNA 调控的复杂性，并表明对这种控制的全面理解仍然是一个挑战。然而，也很可能这种理解将有助于阐明 RNA 加工调控的新机制。
