PMID- 33634165
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210227
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 7
DP  - 2020
TI  - Silencing of the tRNA Modification Enzyme Cdkal1 Effects Functional Insulin 
      Synthesis in NIT-1 Cells: tRNA(Lys3) Lacking ms(2)- (ms(2)t(6)A(37)) is Unable to 
      Establish Sufficient Anticodon:Codon Interactions to Decode the Wobble Codon AAG.
PG  - 584228
LID - 10.3389/fmolb.2020.584228 [doi]
LID - 584228
AB  - Human Genome Wide Association Studies found a significant risk of Type 2 Diabetes 
      Mellitus (T2DM) in single nucleotide polymorphisms in the cdkal1 gene. The cdkal1 
      gene is remote from the insulin gene and with the surprising function of a 
      specific tRNA modification. Population studies and case control studies acquired 
      evidences of the connection between Cdkal1 protein and insulin production over 
      the years. To obtain biochemical proofs directly linking potential SNPs to their 
      roles in insulin production and availability is challenging, but the development 
      of Cdkal1 knock out mice and knock out cell lines made it possible to extend our 
      knowledge towards therapeutic field of diabetic research. Supporting the 
      evidences, here we show that knock down of the cdkal1 gene using small 
      interfering and short hairpin RNA in the NIT-1 cell line, a beta-cell line inducible 
      for insulin resulted in reduced levels of cdkal1 and mature insulin mRNAs, 
      increased the level of precursor insulin mRNA, decreased Cdkal1 and insulin 
      proteins, and diminished modification of tRNA(Lys3) from t(6)A(37) to 
      ms(2)t(6)A(37), the specified function of Cdkal1. tRNA(Lys3) lacking ms(2)- is 
      incapable of establishing sufficient hydrogen bonding energy and hydrophobic 
      stabilization to decode the wobble codon AAG.
CI  - Copyright (c) 2021 Narendran, Vangaveti, Ranganathan, Eruysal, Craft, Alrifai, 
      Chua, Sarachan, Litwa, Ramachandran and Agris.
FAU - Narendran, Amithi
AU  - Narendran A
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
FAU - Vangaveti, Sweta
AU  - Vangaveti S
AD  - Program in Bioinformatics and Integrative Biology, University of Massachusetts 
      Medical School, Worcester, MA, United States.
FAU - Ranganathan, Srivathsan V
AU  - Ranganathan SV
AD  - Knight Cancer Institute, Oregon Health Sciences, School of Medicine, Portland, 
      OR, United States.
FAU - Eruysal, Emily
AU  - Eruysal E
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
FAU - Craft, Miranda
AU  - Craft M
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
FAU - Alrifai, Omar
AU  - Alrifai O
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
FAU - Chua, Fu Yee
AU  - Chua FY
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
FAU - Sarachan, Kathryn
AU  - Sarachan K
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
FAU - Litwa, Breann
AU  - Litwa B
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
FAU - Ramachandran, Sheetal
AU  - Ramachandran S
AD  - Department of Medicine, Duke University School of Medicine, Durham, NC, United 
      States.
FAU - Agris, Paul F
AU  - Agris PF
AD  - The RNA Institute and Department of Biological Sciences, University of Albany, 
      Albany, NY, United States.
AD  - Department of Medicine, Duke University School of Medicine, Durham, NC, United 
      States.
LA  - eng
PT  - Journal Article
DEP - 20210209
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC7900539
OTO - NOTNLM
OT  - CDKAL1
OT  - Cdkal1 protein
OT  - Type 2 diabetes
OT  - Wobble decoding on the ribosome
OT  - insulin
OT  - tRNA modification
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/27 06:00
MHDA- 2021/02/27 06:01
PMCR- 2020/01/01
CRDT- 2021/02/26 06:04
PHST- 2020/07/16 00:00 [received]
PHST- 2020/12/31 00:00 [accepted]
PHST- 2021/02/26 06:04 [entrez]
PHST- 2021/02/27 06:00 [pubmed]
PHST- 2021/02/27 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 584228 [pii]
AID - 10.3389/fmolb.2020.584228 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 Feb 9;7:584228. doi: 10.3389/fmolb.2020.584228. 
      eCollection 2020.