Protein arginine methylation: Cellular functions and methods of analysis

ArticleinBiochimica et Biophysica Acta 1764(12):1890-903 · January 2007with30 Reads
DOI: 10.1016/j.bbapap.2006.08.008 · Source: PubMed
Abstract
During the last few years, new members of the growing family of protein arginine methyltransferases (PRMTs) have been identified and the role of arginine methylation in manifold cellular processes like signaling, RNA processing, transcription, and subcellular transport has been extensively investigated. In this review, we describe recent methods and findings that have yielded new insights into the cellular functions of arginine-methylated proteins, and we evaluate the currently used procedures for the detection and analysis of arginine methylation.
    • "The interactions of RGG/RG motifs with RNA molecules are believed to be based on the arginine's positive charge but also on hydrophobic interactions . Accordingly, the improved binding of AUF1 p45 aDMA to the WNV RNA (Fig. 6A) may, to some extent, be related to a methylation-caused increment of the local basicity and hydrophobicity of the arginine residues (Bedford and Richard 2005; Pahlich et al. 2006). However, our data clearly show that the methylation of AUF1 p45 did not generally enhance the protein's RNA binding capacity because both the methylated and nonmethylated AUF1 p45 variants show a similar high affinity to the AU-rich element in the upstream portion of the WNV 3 ′ UTR and a comparable low affinity to unrelated RNA molecules (Fig. 6A). "
    [Show abstract] [Hide abstract] ABSTRACT: A prerequisite for the intracellular replication process of the Flavivirus West Nile virus (WNV) is the cyclization of the viral RNA genome, which enables the viral replicase to initiate RNA synthesis. Our earlier studies indicated that the p45 isoform of the cellular AU-rich element binding protein 1 (AUF1) has an RNA chaperone activity, which supports RNA cyclization and viral RNA synthesis by destabilizing a stem structure at the WNV RNA's 3'-end. Here we show that in mammalian cells, AUF1 p45 is consistently modified by arginine methylation of its C terminus. By a combination of different experimental approaches, we can demonstrate that the methyltransferase PRMT1 is necessary and sufficient for AUF1 p45 methylation and that PRMT1 is required for efficient WNV replication. Interestingly, in comparison to the nonmethylated AUF1 p45, the methylated AUF1 p45(aDMA) exhibits a significantly increased affinity to the WNV RNA termini. Further data also revealed that the RNA chaperone activity of AUF1 p45(aDMA) is improved and the methylated protein stimulates viral RNA synthesis considerably more efficiently than the nonmethylated AUF1 p45. In addition to its destabilizing RNA chaperone activity, we identified an RNA annealing activity of AUF1 p45, which is not affected by methylation. Arginine methylation of AUF1 p45 thus represents a specific determinant of its RNA chaperone activity while functioning as a WNV host factor. Our data suggest that the methylation modifies the conformation of AUF1 p45 and in this way affects its RNA binding and restructuring activities.
    Full-text · Article · Aug 2016
    • "Besides lysine methylation, arginine methylation is also known to modulate gene expression in many organisms. Protein Arginine Methyltransferase 5 (PRMT5) is a member of a protein family that catalyzes arginine methylation, a common post-translational modification that occurs in eukaryotes and regulates a myriad of processes through its effects on proteins involved in the modulation of chromatin structure, transcription, RNA processing, signal transduction and cellular differentiation, among other processes [100][101][102][103][104][105]. PRMT5 has been shown to modulate circadian rhythms in both plants and flies. "
    [Show abstract] [Hide abstract] ABSTRACT: The circadian clock drives rhythms in multiple physiological processes allowing plants to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of thousands of genes linked to the control of photosynthesis, cell elongation, biotic and abiotic stress responses, developmental processes such as flowering, and the clock itself. Given its pervasive effects on plant physiology, it is not surprising that circadian clock genes have played an important role in the domestication of crop plants and in the improvement of crop productivity. Therefore, identifying the principles governing the dynamics of the circadian gene regulatory network in plants could strongly contribute to further speed up crop improvement. Here we provide an historical as well as a current description of our knowledge of the molecular mechanisms underlying circadian rhythms in plants. This work focuses on the transcriptional and post-transcriptional regulatory layers that control the very core of the circadian clock, and some of its complex interactions with signaling pathways that help synchronize plant growth and development to daily and seasonal changes in the environment.
    Full-text · Article · Jul 2016
    • "In fact, several of these studies showed that PRMT4 and PRMT5 simultaneously control myogenesis, with both proteins having similar positive roles in the control of expression of genes known to play a key role regulating this developmental process1920212223. This is at odds with the current view that assumes that PRMT4, a type I PRMT, acts as a co-activator of gene expression, while PRMT5, the main type II PRMT, acts as a transcriptional repressor [3,4,10,24]. Whether the similar positive role that PRMT5 and PRMT4 play in the control of myogenesis is the exception or the rule is not known. "
    [Show abstract] [Hide abstract] ABSTRACT: Methylation at arginine residues (R) is an important post-translational modification that regulates a myriad of essential cellular processes in eukaryotes, such as transcriptional regulation, RNA processing, signal transduction and DNA repair. Arginine methylation is catalyzed by a family of enzymes known as protein arginine methyltransferases (PRMTs). PRMTs are classified as Type I or Type II, depending on the position of the methyl group on the guanidine of the methylated arginine. Previous reports have linked symmetric R methylation to transcriptional repression, while asymmetric R methylation is generally associated with transcriptional activation. However, global studies supporting this conclusion are not available. Here we compared side by side the physiological and molecular roles of the best characterized plant PRMTs, the Type II PRMT5 and the Type I PRMT4, also known as CARM1 in mammals. We found that prmt5 and prmt4a;4b mutants showed similar alterations in flowering time, photomorphogenic responses and salt stress tolerance, while only prmt5 mutants exhibited alterations in circadian rhythms. An RNA-seq analysis revealed that expression and splicing of many differentially regulated genes was similarly enhanced or repressed by PRMT5 and PRMT4s. Furthermore, PRMT5 and PRMT4s co-regulated the expression and splicing of key regulatory genes associated with transcription, RNA processing, responses to light, flowering, and abiotic stress tolerance, being candidates to mediate the physiological alterations observed in the mutants. Our global analysis indicates that two of the most important Type I and Type II arginine methyltransferases, PRTM4 and PRMT5, have mostly overlapping as well as specific, but not opposite, roles in the global regulation of gene expression in plants.
    Full-text · Article · Dec 2015
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