Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
Gene. 2013 Dec 1;531(2):126-32. doi: 10.1016/j.gene.2012.09.111. Epub 2012 Oct 12.
Pulmonary surfactant protein A (SP-A) plays a key role in innate lung host defense, in surfactant-related functions, and in parturition. In the course of evolution, the genetic complexity of SP-A has increased, particularly in the regulatory regions (i.e. promoter, untranslated regions). Although most species have a single SP-A gene, two genes encode SP-A in humans and primates (SFTPA1 and SFTPA2). This may account for the multiple functions attributed to human SP-A, as well as the regulatory complexity of its expression by a relatively diverse set of protein and non-protein cellular factors. The interplay between enhancer cis-acting DNA sequences and trans-acting proteins that recognize these DNA elements is essential for gene regulation, primarily at the transcription initiation level. Furthermore, regulation at the mRNA level is essential to ensure proper physiological levels of SP-A under different conditions. To date, numerous studies have shown significant complexity of the regulation of SP-A expression at different levels, including transcription, splicing, mRNA decay, and translation. A number of trans-acting factors have also been described to play a role in the control of SP-A expression. The aim of this report is to describe the genetic complexity of the SFTPA1 and SFTPA2 genes, as well as to review regulatory mechanisms that control SP-A expression in humans and other animal species.
肺表面活性物质蛋白 A（SP-A）在先天肺宿主防御、表面活性物质相关功能以及分娩中起着关键作用。在进化过程中，SP-A 的遗传复杂性增加了，特别是在调节区域（即启动子、非翻译区）。尽管大多数物种只有一个 SP-A 基因，但人类和灵长类动物有两个基因编码 SP-A（SFTPA1 和 SFTPA2）。这可能解释了人类 SP-A 的多种功能，以及其表达的调控复杂性，由相对多样化的蛋白质和非蛋白质细胞因子组成。增强子顺式作用 DNA 序列与识别这些 DNA 元件的反式作用蛋白之间的相互作用对于基因调控至关重要，主要在转录起始水平。此外，mRNA 水平的调节对于确保在不同条件下 SP-A 的适当生理水平也是必不可少的。迄今为止，许多研究表明 SP-A 表达在不同水平（包括转录、剪接、mRNA 降解和翻译）的调控具有显著的复杂性。一些反式作用因子也被描述为在 SP-A 表达的控制中发挥作用。本报告的目的是描述 SFTPA1 和 SFTPA2 基因的遗传复杂性，并综述调控人类和其他动物物种 SP-A 表达的机制。
