探索RNA |Overview
RNA从阴影中出来
当Covid-19疫苗推动RNA进入敏捷的时候，科学家们非常了解其潜力。有时，如甲基等化学物质加入到RNA的表面上，使其能够提高蛋白质产生的力量。但如果添加了太多，我们的健康会受到影响。
Two of our investigators are studying these modified RNAs to help understand diseases and to guide treatment development.
理查德格雷戈里，博士，建立他的发现，当RNA获得比所需的更多甲基化合物，细胞分裂爆炸，触发癌症。相反，太少的甲基干扰了儿童发育，导致神经系统疾病，例如侏儒症和小头畸形（小脑）。
瑞恩·弗林，MD，博士，发现RNA一旦被认为完全存在于细胞内，可以与糖分子结合，在细胞表面上制作一个家。无论这个位置是否提供了具有新型治疗力的RNA或升高疾病脆弱性 - 或两者都是他的研究的重点。
RNA和癌症
In an important discovery, Dr. Gregory found that cancer can result when a small piece of genetic code is disrupted in non-coding RNA. He then found that other alterations to RNA could fuel cancer as well. "We now appreciate that, like DNA, RNA—the intermediate between the gene and the protein—can be "modified" [by chemical additions]," says Dr. Gregory. These changes are mostly helpful but can also wreak havoc.
例如，酶MetT13将甲基添加到信使RNA至微调基因表达。但是，正如他第一次意识到的那样，MetT13在癌症中表现错了 - 过多可以引发癌症，例如急性髓性白血病。从那时起，该团队鉴定了第二酶MetT11，其锁定在转移RNA-TRNA上 - 在将基因转化为蛋白质的最终步骤中使用的RNA的类型。与METTL3一样，大量可以引发癌症 - 在这种情况下，脂肪瘤或胶质母细胞瘤。
New drug targets for cancer
癌细胞需要MetT1和MetT1，比健康的细胞更多。“如果我们在血液干细胞中敲出MetT13，它们就会才能罚款。但如果你在急性髓性白血病细胞中击倒它，他们就会死，”格雷戈里博士说。
可以沉默MetT1或MetT11的药物可能能够将这些癌症脱落。这就是为什么团队在试管中测试几个候选人。他们没有停下来。
“知道METTL1的化学结构和满足TL3 allowed us to design computational models to look at millions of compounds, searching for one that can spark the desired chemical reaction," says Dr. Gregory. Next, they hope to test promising candidates in cancer cell lines and preclinical models. "Our goal is to partner with clinicians and move promising candidates toward the clinic over the next several years," he says.
Meet our new RNA expert
Dr. Ryan Flynn discusses his research in a short video
Viewing RNA from a new vantage point
现在我们知道RNA可以在细胞表面上茁壮成长，一种新的可能性前沿展开。RNA可以从它的栖息地在细胞顶部的栖息地，它不能从内部做，并且如何习惯我们的优势？
Dr. Flynn points out that RNA is a flexible platform. It can bind to molecules, shut down or enhance cell-to-cell communication, or help cells hide from the immune system. Because it is so versatile, Dr. Flynn thinks we should be able to tweak it in ways that can help us combat disease.
We now have three ‘hands’ on the cell surface. From left to right, a glycoprotein, a glycolipid, and the newly discovered glycoRNA. (Illustration: Ryan Flynn/Sebastian Stankiewicz, Boston Children’s Hospital)
“例如，血液癌症可能在细胞表面上具有太多的糖RNA [甘草果酱]，这可能导致癌症。我们可以制定治疗，以切断细胞表面的RNA，降低癌症生长，”他说。
In short, by developing glycoRNA-based therapies, we may be able to address a myriad of diseases by enhancing or blocking cell-surface glycoRNAs on diseased cells.
RNA和自身免疫性疾病：未来的一个话题
我们的细胞表面覆盖脂质，糖和蛋白质，有助于来回传输信号。但有时候不需要的访客侵入，触发免疫细胞迁入和攻击。在自身免疫性疾病（如狼疮）中，RNA可以被误标配为“冒名参加”并袭击。
直到Flynn博士发现RNA可以居住在细胞内外，目前还不清楚免疫系统如何如何追踪细胞内部 - 可以找到杀死它的RNA。
“知道RNA可以进入细胞表面改变我们对自身免疫疾病的看法，并为我们提供了关于如何对待它们的新想法，”Flynn博士说。
While many questions remain regarding the roots of autoimmune disease, we are certain Dr. Flynn's investigations will bring some resolution in the coming years.
