PMID- 32279998
OWN - NLM
STAT- MEDLINE
DCOM- 20201124
LR  - 20201124
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 526
IP  - 4
DP  - 2020 Jun 11
TI  - The 5' untranslated region of the anti-apoptotic protein Survivin contains an 
      inhibitory upstream AUG codon.
PG  - 898-905
LID - S0006-291X(20)30658-6 [pii]
LID - 10.1016/j.bbrc.2020.03.160 [doi]
AB  - Survivin (BIRC5) is an anti-apoptotic protein that is important in cancer. 
      Mechanisms responsible for controlling Survivin levels in cells include 
      transcriptional regulation and modulation of protein stability via 
      post-translational modifications; however to date, translational control has been 
      poorly studied. Here, we focused particularly on the primary control elements 
      present in the Survivin 5' untranslated region (5'UTR). Bioinformatic analysis of 
      ribosome occupancy on the Survivin 5'UTR revealed the presence of elongating 
      ribosomes upstream of the canonical initiator AUG, suggesting an alternative 
      upstream initiator AUG (uAUG) might exist. This uAUG was found out-of-frame at 
      position -71 and appeared as a conserved element in mammals. RACE analysis 
      revealed different transcriptional start sites for BIRC5, which indicated that 
      translational control by this uAUG is restricted to longer 5'UTR variants. We 
      studied the activity of the uAUG in different cell types by cloning the Survivin 
      5'UTR DNA sequence (wild-type and mutated variants) upstream of renilla 
      luciferase (RLuc) into a pcDNA3 plasmid. Changes in RLuc activity were determined 
      by luminescence assays and Western blotting. Results showed that when this uAUG 
      was mutated to AUU or AGG in the cloned Survivin 5'UTR, RLuc activity was 
      significantly increased. Similar results were obtained when uAUG was positioned 
      inframe with the RLuc initiator AUG. Immunodetection of Renilla (35 kDa) by 
      Western blotting revealed the presence of a second band (37 kDa approximately) in 
      cells transfected with the Inframe reporter constructs, indicating that the uAUG 
      was functional in our experimental conditions. In conclusion, our experimental 
      data demonstrate the presence of an alternative and inhibitory initiator uAUG in 
      the Survivin 5' UTR. This inhibitory uAUG may help understanding how Survivin 
      expression is downregulated under physiological or pathological conditions.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Palavecino, Christian E
AU  - Palavecino CE
AD  - Laboratorio de Microbiologia Celular, Instituto de Investigacion e Innovacion en 
      Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord 
      Cochrane 418, Santiago, 8320000, Chile.
FAU - Carrasco-Veliz, Nicolas
AU  - Carrasco-Veliz N
AD  - Laboratorio de Microbiologia Celular, Instituto de Investigacion e Innovacion en 
      Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord 
      Cochrane 418, Santiago, 8320000, Chile.
FAU - Quest, Andrew F G
AU  - Quest AFG
AD  - Centro de Estudios Avanzados en Enfermedades Cronicas (ACCDiS), Sergio 
      Livingstone 1007, Independencia, 8380492, Santiago, Chile; Laboratorio de 
      Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer 
      (CEMC), Instituto de Ciencias Biomedicas (ICBM), Facultad de Medicina, 
      Universidad de Chile, Avenida Independencia 1027, Independencia, 8380453, Chile.
FAU - Garrido, Maritza P
AU  - Garrido MP
AD  - Laboratorio de Endocrinologia y Biologia de la Reproduccion, Departamento de 
      Obstetricia y Ginecologia, Hospital Clinico Universidad de Chile, Avenida Santos 
      Dumont 999, Independencia, 8380456, Chile.
FAU - Valenzuela-Valderrama, Manuel
AU  - Valenzuela-Valderrama M
AD  - Laboratorio de Microbiologia Celular, Instituto de Investigacion e Innovacion en 
      Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord 
      Cochrane 418, Santiago, 8320000, Chile; Centro de Estudios Avanzados en 
      Enfermedades Cronicas (ACCDiS), Sergio Livingstone 1007, Independencia, 8380492, 
      Santiago, Chile. Electronic address: manuel.valenzuela@ucentral.cl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200409
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Codon, Initiator)
RN  - 0 (Survivin)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Animals
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Codon, Initiator/*genetics
MH  - Conserved Sequence/genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Luciferases/metabolism
MH  - Mammals/genetics
MH  - Open Reading Frames/genetics
MH  - Protein Biosynthesis/genetics
MH  - Survivin/*genetics
OTO - NOTNLM
OT  - 5'UTR
OT  - Helicobacter pylori
OT  - RACE
OT  - Survivin
OT  - uAUG
EDAT- 2020/04/14 06:00
MHDA- 2020/11/25 06:00
CRDT- 2020/04/14 06:00
PHST- 2020/03/13 00:00 [received]
PHST- 2020/03/28 00:00 [accepted]
PHST- 2020/04/14 06:00 [pubmed]
PHST- 2020/11/25 06:00 [medline]
PHST- 2020/04/14 06:00 [entrez]
AID - S0006-291X(20)30658-6 [pii]
AID - 10.1016/j.bbrc.2020.03.160 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Jun 11;526(4):898-905. doi: 
      10.1016/j.bbrc.2020.03.160. Epub 2020 Apr 9.