Addition to the genome
Several hundred new genes have been discovered in the human genome
American geneticists have discovered several hundred previously unknown genes in the least studied parts of the human genome. It turned out that more than 50 of them produce proteins that are involved in the development of cancer cells. The results of the study are published in the journal Nature Biotechnology (Prensner et al., Noncanonical open reading frames encode functional proteins essential for cancer cell survival – VM).
At the moment, about 20 thousand genes have been identified in the human genome. Early analyses of the human genome sequence suggested the existence of more than one hundred thousand protein-coding genes, but further studies have shown that most of these candidate genes most likely produce non-coding RNAs, fragmented complementary DNA and RNA clones expressed at insignificant levels.
The current NeXtProt Human proteome project database contains approximately 17,600 protein-coding genes confirmed by mass spectrometry and about 2,100 unconfirmed protein-coding genes.
Nevertheless, there is more and more evidence that in genes that are currently annotated as non–coding RNAs or pseudogenes, as well as those located in some untranslated regions, translation takes place - the process of protein synthesis from amino acids on the matrix of informational (matrix) RNA, carried out by a special cellular organelle ribosome. However, until now there has been no systematic experimental confirmation of whether the proteins arising from such translation are biologically functional.
Researchers from the Broad Institute Harvard University and The Massachusetts Institute of Technology, the largest center for genomics and the implementation of the Human Genome project, experimentally tested 553 candidate genes, as which the authors considered the Open Reading Frame (ORF) – sequences of nucleotides in the composition of long non–coding RNAs.
Candidate genes were selected based on published data predicting ORF, potentially capable of encoding biologically active proteins. At the same time, pseudogenes and ORFs, which are variants of already known protein-coding regions, were excluded from the analysis.
In experiments on ectopic expression – gene expression in an unusual place in the body – 257 ORFs showed signs of protein expression and 401 induced changes in gene expression. Of these, 57 contributed to the viability of human cancer cells.
In particular, the researchers found that one of these ORFs – G029442 – encodes glycine-rich extracellular protein-1 (GREP1), which has an increased content of oncogenic cytokine GDF15 and is highly expressed in breast cancer. Blocking it with a special inhibitor mitigated the effect of cancer cell development in 263 lines.
The authors believe that biologically active proteins expressed by non-canonical ORFs may become potential targets for the development of new cancer treatments.
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