PMID- 21840962
OWN - NLM
STAT- MEDLINE
DCOM- 20111222
LR  - 20211020
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 301
IP  - 5
DP  - 2011 Nov
TI  - The untranslated exon B of human surfactant protein A2 mRNAs is an enhancer for 
      transcription and translation.
PG  - L795-803
LID - 10.1152/ajplung.00439.2010 [doi]
AB  - Two human genes, SFTPA1 (SP-A1) and SFTPA2 (SP-A2), encode surfactant protein A, 
      a molecule of innate immunity and surfactant-related functions. Several genetic 
      variants have been identified for both genes. These include nucleotide (nt) 
      polymorphisms, as well as alternative splicing patterns at the 5' untranslated 
      region (5'UTR). Exon B (eB) is included in the 5'UTR of most SP-A2, but not SP-A1 
      splice variants. We investigated the role of eB in the regulation of gene 
      expression and translation efficiency. A luciferase (Luc) reporter gene was 
      cloned downstream of the entire (AeBD) or eB deletion mutants (del_mut) of the 
      SP-A2 5'UTR, or heterologous 5'UTRs containing the eB sequence, or a random 
      sequence of equal length. The del_mut constructs consisted in consecutive 
      deletions of five nucleotides (n = 8) within eB and the exon-exon junctions in 
      the AeBD 5'UTR. Luc activities and mRNA levels were compared after transfection 
      of NCI-H441 cells. We found that 1) eB increased Luc mRNA levels when placed 
      upstream of heterologous 5'UTR sequences or the promoter region, regardless of 
      its position and orientation; 2) translation efficiency of in vitro-generated 
      mRNAs containing eB was higher than that of mRNAs without eB; and 3) the 
      integrity of eB sequence is crucial for transcription and translation of the 
      reporter gene. Thus eB 1) is a transcription enhancer, because it increases mRNA 
      content regardless of position and orientation, 2) enhances translation when 
      placed in either orientation within its natural 5'UTR sequence and in 
      heterologous 5'UTRs, and 3) contains potential regulatory elements for both 
      transcription and translation. We conclude that eB sequence and length are 
      determinants of transcription and translation efficiency.
FAU - Silveyra, Patricia
AU  - Silveyra P
AD  - Center for Host Defense, Inflammation, and Lung Disease Research, Department of 
      Pediatrics, Hershey, Pennsylvania 17033-0850, USA.
FAU - Raval, Manmeet
AU  - Raval M
FAU - Simmons, Brett
AU  - Simmons B
FAU - Diangelo, Susan
AU  - Diangelo S
FAU - Wang, Guirong
AU  - Wang G
FAU - Floros, Joanna
AU  - Floros J
LA  - eng
GR  - HL-34788/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110812
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Pulmonary Surfactant-Associated Protein A)
RN  - 0 (SFTPA2 protein, human)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Adenocarcinoma/*genetics/metabolism/pathology
MH  - Alternative Splicing
MH  - Cell Line, Tumor
MH  - *Exons
MH  - Genes, Reporter
MH  - Humans
MH  - Luciferases/analysis
MH  - Lung Neoplasms/*genetics/metabolism/pathology
MH  - Molecular Sequence Data
MH  - Plasmids
MH  - Protein Biosynthesis/*genetics
MH  - Pulmonary Surfactant-Associated Protein A/chemistry/*genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Regulatory Sequences, Nucleic Acid
MH  - Sequence Deletion
MH  - *Transcription, Genetic
MH  - Transfection
PMC - PMC3290452
EDAT- 2011/08/16 06:00
MHDA- 2011/12/23 06:00
PMCR- 2012/11/01
CRDT- 2011/08/16 06:00
PHST- 2011/08/16 06:00 [entrez]
PHST- 2011/08/16 06:00 [pubmed]
PHST- 2011/12/23 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - ajplung.00439.2010 [pii]
AID - L-00439-2010 [pii]
AID - 10.1152/ajplung.00439.2010 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2011 Nov;301(5):L795-803. doi: 
      10.1152/ajplung.00439.2010. Epub 2011 Aug 12.