Abstract:
:In addition to acting as template for protein synthesis, messenger RNA (mRNA) often contains sensory sequence elements that regulate this process. Here we report a new mechanism that limits the number of complete protein molecules that can be synthesized from a single mRNA molecule of the human AMD1 gene encoding adenosylmethionine decarboxylase 1 (AdoMetDC). A small proportion of ribosomes translating AMD1 mRNA stochastically read through the stop codon of the main coding region. These readthrough ribosomes then stall close to the next in-frame stop codon, eventually forming a ribosome queue, the length of which is proportional to the number of AdoMetDC molecules that were synthesized from the same AMD1 mRNA. Once the entire spacer region between the two stop codons is filled with queueing ribosomes, the queue impinges upon the main AMD1 coding region halting its translation. Phylogenetic analysis suggests that this mechanism is highly conserved in vertebrates and existed in their common ancestor. We propose that this mechanism is used to count and limit the number of protein molecules that can be synthesized from a single mRNA template. It could serve to safeguard from dysregulated translation that may occur owing to errors in transcription or mRNA damage.
journal_name
Naturejournal_title
Natureauthors
Yordanova MM,Loughran G,Zhdanov AV,Mariotti M,Kiniry SJ,O'Connor PBF,Andreev DE,Tzani I,Saffert P,Michel AM,Gladyshev VN,Papkovsky DB,Atkins JF,Baranov PVdoi
10.1038/nature25174subject
Has Abstractpub_date
2018-01-18 00:00:00pages
356-360issue
7688eissn
0028-0836issn
1476-4687pii
nature25174journal_volume
553pub_type
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