Zhou Q, Guo Y, Liu Y
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA.
Mol Cell Biol. 1998 Feb;18(2):815-26. doi: 10.1128/MCB.18.2.815.
The heat-stable antigen (HSA) is a costimulatory molecule for T-cell activation. Its expression is strictly regulated during lymphocyte development and differentiation. Recent studies using HSA-transgenic mice have demonstrated that this regulated expression is critical for normal development of T and B lymphocytes. However, the mechanisms that control the expression of HSA are largely unknown. HSA mRNA is comprised of a 0.23-kb open reading frame and a 1.5-kb 3' untranslated region (3'UTR). The function of the long 3'UTR has not been addressed. Here we investigate the role of the 3'UTR of HSA mRNA. We show that a 160-bp element, located in the region of nucleotides 1465 to 1625 in the 3'UTR of HSA mRNA, promotes RNA degradation and that this effect is neutralized by a 43-bp fragment approximately 1 kb upstream of the negative cis element. Both positive and negative cis elements in the HSA mRNA are distinct from other sequences that are known to modulate mRNA stability. These results provide direct evidence that the interplay between two novel cis elements in the 3'UTR of HSA mRNA determines cell surface HSA expression by modulating its RNA stability.
热稳定抗原（HSA）是一种用于T细胞激活的共刺激分子。其表达在淋巴细胞发育和分化过程中受到严格调控。最近使用HSA转基因小鼠的研究表明，这种调控表达对于T和B淋巴细胞的正常发育至关重要。然而，控制HSA表达的机制在很大程度上尚不清楚。HSA mRNA由一个0.23 kb的开放阅读框和一个1.5 kb的3'非翻译区（3'UTR）组成。长3'UTR的功能尚未得到研究。在此，我们研究了HSA mRNA 3'UTR的作用。我们发现，位于HSA mRNA 3'UTR中核苷酸1465至1625区域的一个160 bp元件可促进RNA降解，而这种效应被一个位于负性顺式元件上游约1 kb处的43 bp片段所中和。HSA mRNA中的正性和顺式元件均与已知调节mRNA稳定性的其他序列不同。这些结果提供了直接证据，表明HSA mRNA 3'UTR中两个新的顺式元件之间的相互作用通过调节其RNA稳定性来决定细胞表面HSA的表达。
