PMID- 34113740
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210621
IS  - 2452-0144 (Print)
IS  - 2452-0144 (Electronic)
IS  - 2452-0144 (Linking)
VI  - 18
DP  - 2020 Mar
TI  - Serotonin transporter untranslated regions influence mRNA abundance and protein 
      expression.
LID - 100513 [pii]
LID - 10.1016/j.genrep.2019.100513 [doi]
AB  - The serotonin transporter (SERT, SLC6A4) is a Na(+)-dependent transporter that 
      regulates the availability of serotonin (5-HT, 5-hydroxytryptamine), a key 
      neurotransmitter and hormone in the brain and the intestine. The human SERT gene 
      consists of two alternate promoters that drive expression of an identical SERT 
      protein. However, there are different mRNA transcript variants derived from these 
      two promoters that differ in their 5' untranslated region (5'UTR), which is the 
      region of the mRNA upstream from the protein-coding region. Two of these 
      transcripts contain exon-1a and are abundant in neuronal tissue, whereas the 
      third transcript contains exon-1c and is abundant in the intestine. The 3'UTR is 
      nearly identical among the transcripts. Current studies tested the hypothesis 
      that the UTRs of SERT influence its expression in intestinal epithelial cells 
      (IECs) by controlling mRNA or protein levels. The SERT UTRs were cloned into 
      luciferase reporter plasmids and luciferase mRNA and activity were measured 
      following transient transfection of the UTR constructs into the model IEC Caco-2. 
      Luciferase activity and mRNA abundance were higher than the empty vector for two 
      of the three 5'UTR variants. Calculation of translation index (luciferase 
      activity divided by the relative luciferase mRNA level) revealed that the exon-1a 
      containing 5'UTRs had enhanced translation when compared to the exon-1c 
      containing 5'UTR which exhibited a low translation efficiency. Compared to the 
      empty vector, the SERT 3'UTR markedly decreased luciferase activity. In silico 
      analysis of the SERT 3'UTR revealed many conserved potential miRNA binding sites 
      that may be responsible for this decrease. In conclusion, we have shown that the 
      UTRs of SERT regulate mRNA abundance and protein expression. Delineating the 
      molecular basis by which the UTRs of SERT influence its expression will lead to 
      an increased understanding of post-transcriptional regulation of SERT in GI 
      disorders associated with altered 5-HT availability.
FAU - Manzella, Christopher
AU  - Manzella C
AD  - Department of Physiology & Biophysics, University of Illinois at Chicago, 
      Chicago, IL, United States of America.
FAU - Singhal, Megha
AU  - Singhal M
AD  - Division of Gastroenterology & Hepatology, University of Illinois at Chicago, 
      Chicago, IL, United States of America.
FAU - Ackerman, Max
AU  - Ackerman M
AD  - University of Illinois at Chicago, College of Liberal Arts and Sciences, United 
      States of America.
FAU - Alrefai, Waddah A
AU  - Alrefai WA
AD  - Division of Gastroenterology & Hepatology, University of Illinois at Chicago, 
      Chicago, IL, United States of America.
AD  - Jesse Brown VA Medical Center, Chicago, IL, United States of America.
FAU - Saksena, Seema
AU  - Saksena S
AD  - Division of Gastroenterology & Hepatology, University of Illinois at Chicago, 
      Chicago, IL, United States of America.
AD  - Jesse Brown VA Medical Center, Chicago, IL, United States of America.
FAU - Dudeja, Pradeep K
AU  - Dudeja PK
AD  - Division of Gastroenterology & Hepatology, University of Illinois at Chicago, 
      Chicago, IL, United States of America.
AD  - Jesse Brown VA Medical Center, Chicago, IL, United States of America.
FAU - Gill, Ravinder K
AU  - Gill RK
AD  - Division of Gastroenterology & Hepatology, University of Illinois at Chicago, 
      Chicago, IL, United States of America.
AD  - Jesse Brown VA Medical Center, Chicago, IL, United States of America.
LA  - eng
GR  - I01 BX002867/BX/BLRD VA/United States
GR  - IK6 BX005243/BX/BLRD VA/United States
GR  - R01 DK098170/DK/NIDDK NIH HHS/United States
GR  - R01 DK092441/DK/NIDDK NIH HHS/United States
GR  - F30 DK113703/DK/NIDDK NIH HHS/United States
GR  - I01 BX000152/BX/BLRD VA/United States
GR  - I01 BX002011/BX/BLRD VA/United States
PT  - Journal Article
DEP - 20191029
PL  - United States
TA  - Gene Rep
JT  - Gene reports
JID - 101680713
PMC - PMC8188842
MID - NIHMS1587889
OTO - NOTNLM
OT  - Intestine
OT  - SERT
OT  - SLC6A4
OT  - Serotonin
OT  - Untranslated regions
COIS- Declaration of competing interest None.
EDAT- 2020/03/01 00:00
MHDA- 2020/03/01 00:01
PMCR- 2021/06/09
CRDT- 2021/06/11 06:49
PHST- 2021/06/11 06:49 [entrez]
PHST- 2020/03/01 00:00 [pubmed]
PHST- 2020/03/01 00:01 [medline]
PHST- 2021/06/09 00:00 [pmc-release]
AID - 100513 [pii]
AID - 10.1016/j.genrep.2019.100513 [doi]
PST - ppublish
SO  - Gene Rep. 2020 Mar;18:100513. doi: 10.1016/j.genrep.2019.100513. Epub 2019 Oct 
      29.