La相关蛋白(LARPs)共有La基序(LaM),随后是RNA识别基序(RRM)。这些统称为La模块,在原型核La蛋白和LARP7中,介导与新生RNA聚合酶III转录本的UUU-3\'OH终止基序的结合。在转向最近发现的LARP1和LARP4的poly(A)相关活性之前,我们简要回顾了La和LARP7对RNA3'末端结合和外切核酸酶保护的活性。LARP1和LARP4共有的两个特征是直接结合poly(A)和胞质poly(A)结合蛋白(PABP,也称为PABPC1)。LARP1,LARP4和其他参与mRNA翻译的蛋白质,去端化,和衰变,包含PAM2基序,对PABP的MLLE域具有可变亲和力。我们讨论了一个模型,其中这些PABP相互作用的活动有助于poly(A)修剪活性mRNP。SARS-CoV-2RNA病毒靶向PABP的证据,还简要回顾了控制mRNP活性的LARP1,LARP4和LARP4B。最近的数据表明,LARP4通过稳定mRNApoly(A)尾巴上的PABP来反对去端化。其他数据表明,LARP1可以保护mRNA免于死蛋白化。这取决于在其La模块中存在的具有独特特征的PAM2基序。因此,而核La和LARP7稳定具有3'oligo(U)的小RNA免于衰变,LARP1和LARP4通过与PABP紧密接触而结合并保护mRNA3'poly(A)尾免受死酶的侵害。缩写:5\'TOP:5\'末端寡嘧啶,LaM:La主题,LARP:La相关蛋白,LARP1:La相关蛋白1,MLLE:小姐,NTR:N端区域,PABP:细胞质聚(A)结合蛋白(PABPC1),PolIII:RNA聚合酶III,PAM2:PABP相互作用基序2,PB:加工体,RRM:RNA识别基序,SG:应力颗粒。
La-related proteins (LARPs) share a La motif (LaM) followed by an RNA recognition motif (RRM). Together these are termed the La-module that, in the prototypical nuclear La protein and LARP7, mediates binding to the UUU-3\'OH termination motif of nascent RNA polymerase III transcripts. We briefly review La and LARP7 activities for RNA 3\' end binding and protection from exonucleases before moving to the more recently uncovered poly(A)-related activities of LARP1 and LARP4. Two features shared by LARP1 and LARP4 are direct binding to poly(A) and to the cytoplasmic poly(A)-binding protein (
PABP, also known as PABPC1). LARP1, LARP4 and other proteins involved in mRNA translation, deadenylation, and decay, contain PAM2 motifs with variable affinities for the MLLE domain of PABP. We discuss a model in which these
PABP-interacting activities contribute to poly(A) pruning of active mRNPs. Evidence that the SARS-CoV-2 RNA virus targets
PABP, LARP1, LARP 4 and LARP 4B to control mRNP activity is also briefly reviewed. Recent data suggests that LARP4 opposes deadenylation by stabilizing
PABP on mRNA poly(A) tails. Other data suggest that LARP1 can protect mRNA from deadenylation. This is dependent on a PAM2 motif with unique characteristics present in its La-module. Thus, while nuclear La and LARP7 stabilize small RNAs with 3\' oligo(U) from decay, LARP1 and LARP4 bind and protect mRNA 3\' poly(A) tails from deadenylases through close contact with PABP.Abbreviations: 5\'TOP: 5\' terminal oligopyrimidine, LaM: La motif, LARP: La-related protein, LARP1: La-related protein 1, MLLE: mademoiselle, NTR: N-terminal region,
PABP: cytoplasmic poly(A)-binding protein (PABPC1), Pol III: RNA polymerase III, PAM2: PABP-interacting motif 2, PB: processing body, RRM: RNA recognition motif, SG: stress granule.