Identification of a quality-control mechanism for mRNA 5'-end capping.
The 7-methylguanosine cap structure at the 5' end of eukaryotic messenger RNAs is a critical determinant of their stability and translational efficiency. It is generally believed that 5'-end capping is a constitutive process that occurs during mRNA maturation and lacks the need for a quality-control mechanism to ensure its fidelity. We recently reported that the yeast Rai1 protein has pyrophosphohydrolase activity towards mRNAs lacking a 5'-end cap. Here we show that, in vitro as well as in yeast cells, Rai1 possesses a novel decapping endonuclease activity that can also remove the entire cap structure dinucleotide from an mRNA. This activity is targeted preferentially towards mRNAs with unmethylated caps in contrast to the canonical decapping enzyme, Dcp2, which targets mRNAs with a methylated cap. Capped but unmethylated mRNAs generated in yeast cells with a defect in the methyltransferase gene are more stable in a rai1-gene-disrupted background. Moreover, rai1Δ yeast cells with wild-type capping enzymes show significant accumulation of mRNAs with 5'-end capping defects under nutritional stress conditions of glucose starvation or amino acid starvation. These findings provide evidence that 5'-end capping is not a constitutive process that necessarily always proceeds to completion and demonstrates that Rai1 has an essential role in clearing mRNAs with aberrant 5'-end caps. We propose that Rai1 is involved in an as yet uncharacterized quality control process that ensures mRNA 5'-end integrity by an aberrant-cap-mediated mRNA decay mechanism.
Jiao
Xinfu
X
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA.
Xiang
Song
S
Oh
Chanseok
C
Martin
Charles E
CE
Tong
Liang
L
Kiledjian
Megerditch
M
D020121:5' Untranslated Regions / Q000235:genetics; D000596:Amino Acids / Q000172:deficiency / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006868:Hydrolysis; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics
D020121:5' Untranslated Regions; D000596:Amino Acids; D009687:Nuclear Proteins; D012315:RNA Caps; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; C473024:Rai1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D006151:Guanosine; C075577:RAT1 protein, S cerevisiae; C016578:7-methylguanosine; C400572:DCP2 protein, S cerevisiae; D004722:Endoribonucleases; D005095:Exoribonucleases; D005947:Glucose
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