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Biological Sciences Colloquium: Control of non-AUG codon translation by eIF5-mimic protein

March 29, 2019 @ 4:00 pm - 5:00 pm

Dr. Madhusudan Dey hosts speaker, Dr. Katsura Asano from the Division of Biology at Kansas State University. Dr. Asano will present a talk entitled ‘Control of non-AUG codon translation by eIF5-mimic protein’. The presentation will begin at 4:00 pm in Lapham Hall N101. Please join us for refreshments outside the lecture hall starting at 3:30 pm.

Presentation abstract:

Translation initiation from non-AUG codons plays important roles in various gene regulation programs. In bacteria, GUG initiation is an integral part of an RNA switch regulating replication protein of plasmids. GUG or UUG initiation is permitted in part by a simpler set of initiation factors than those found in eukaryotes. In contrast, eukaryotes evolved a complex initiation system involving eukaryotic initiation factors (eIFs), allowing more accurate initiation and thereby repressing most events of non-AUG initiation. However, non-AUG translation plays a significant role in human biology, even though the efficiency of initiation by this mechanism is generally considered to be low. An example of such non-AUG translation is repeat-associated non-AUG translation, or RAN translation. RAN translation allows translation of tri- or hexa-nucleotide repeats found in FMR1 or other genes important in normal neronal development. The generation of repeat peptides through RAN translation is thought to contribute to the etiology of mental disieses.

Here we present a suprising finding that the non-AUG initiation rate ranges from <1% to nearly 100% compared to AUG translation, depending on Kozak and other new nucleotide contexts. Mechanistically, this range of non-AUG initiation is controlled in part, by the eIF5-mimic protein (5MP). 5MP represses non-AUG translation by competing with eIF5 for the Met-tRNAi-binding factor eIF2. Thus, eIF5 increases and 5MP decreases translation of NAT1/eIF4G2/DAP5 whose sole start codon is GUG as well as RAN translation from FMR1. Using eIF5 and 5MP1 as tools,  ribosome profiling identifies a handful of new non-AUG initiation sites, some of which serve as sole start codons. We propose that the homeostasis of non-AUG translatome is maintained through balanced expression of eIF5 and 5MP. We discuss the significance of thse findings in the molecular basis of cancer and infectious and neurological diseases.

Details

Date:
March 29, 2019
Time:
4:00 pm - 5:00 pm
Event Category:

Venue

Lapham Hall, N101
3209 N Maryland Ave
Milwaukee, WI 53211 United States
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