Stixová Lenka, Komůrková Denisa, Svobodová Kovaříková Alena, Fagherazzi Paolo, Bártová Eva
Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
Faculty of Science, Masaryk University, Kamenice 753/5, 601 77 Brno, Czech Republic.
Life (Basel). 2021 Jul 8;11(7):669. doi: 10.3390/life11070669.
METTL16 methyltransferase is responsible for the methylation of N-adenosine (mA) in several RNAs. In mouse cells, we showed that the nuclear distribution of METTL16 is cell cycle-specific. In the G1/S phases, METTL16 accumulates to the nucleolus, while in the G2 phase, the level of METTL16 increases in the nucleoplasm. In metaphase and anaphase, there is a very low pool of the METTL16 protein, but in telophase, residual METTL16 appears to be associated with the newly formed nuclear lamina. In A-type lamin-depleted cells, we observed a reduction of METTL16 when compared with the wild-type counterpart. However, METTL16 does not interact with A-type and B-type lamins, but interacts with Lamin B Receptor (LBR) and Lap2α. Additionally, Lap2α depletion caused METTL16 downregulation in the nuclear pool. Furthermore, METTL16 interacted with DDB2, a key protein of the nucleotide excision repair (NER), and also with nucleolar proteins, including TCOF, NOLC1, and UBF1/2, but not fibrillarin. From this view, the METTL16 protein may also regulate the transcription of ribosomal genes because we observed that the high level of mA in 18S rRNA appeared in cells with upregulated METTL16.
METTL16甲基转移酶负责多种RNA中N - 腺苷（mA）的甲基化。在小鼠细胞中，我们发现METTL16的核分布具有细胞周期特异性。在G1/S期，METTL16积聚在核仁中，而在G2期，METTL16在核质中的水平升高。在中期和后期，METTL16蛋白的含量非常低，但在末期，残留的METTL16似乎与新形成的核纤层相关。在A型核纤层蛋白缺失的细胞中，与野生型细胞相比，我们观察到METTL16减少。然而，METTL16不与A型和B型核纤层蛋白相互作用，但与核纤层蛋白B受体（LBR）和Lap2α相互作用。此外，Lap2α的缺失导致核池中METTL16下调。此外，METTL16与核苷酸切除修复（NER）的关键蛋白DDB2相互作用，也与核仁蛋白相互作用，包括TCOF、NOLC1和UBF1/2，但不与纤维原蛋白相互作用。从这个角度来看，METTL16蛋白可能还调节核糖体基因的转录，因为我们观察到18S rRNA中高水平的mA出现在METTL16上调的细胞中。
