Adenylate–uridylate rich element gene transcriptions

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Associate Editor(s)-in-Chief: Henry A. Hoff

"Functionally defined and derived adenylate–uridylate rich element (ARE) consensus sequences have been shown to exist in the 3′UTR of selected mRNAs belonging to interferons, cytokines and proto-oncogenes ( 1 ). A 13-bp ARE motif was computationally derived from a list of functionally labile ARE-mRNAs and was the basis of the ARE-mRNA database (ARED) which contains GenBank entries where the 3′UTR matches the motif ( 2 )."[1]

Human genes

Main article: Human genes

The ARE-mRNA database (ARED) "demonstrated that ARE-mRNAs represent as much as 5–8% of human genes and encode functionally diverse proteins that are important in many transient biological processes including cell growth and differentiation, signal transduction, transcriptional and translational control, hematopoiesis, apoptosis, nutrient transport, and metabolism ( 2 )."[1]

"The 3′UTRs were searched for the 13-bp pattern WWWUAUUUAUWW with mismatch=−1 which was computationally derived as previously described ( 2 ). The pattern was further statistically validated against larger sets of mRNA data (10 872 mRNA with 3′UTR; GenBank 119) showing occurrence of the motif in 6.8% of human mRNA."[1]

"The ARED website ( http://rc.kfshrc.edu.sa/ared ) offers a query search engine that allows searches for ARE-genes using multiple identifier numbers or descriptions such as UniGene IDs, UniGene definition, RefSeq IDs, accession numbers, alternative names, official Gene symbols and mouse homologs (MGD) ( 10 )."[1]

Gene expressions

Main article: Gene expressions

"3′ untranslated regions play an important role in regulating mRNA fate by complexing with RNA binding proteins that help control mRNA localization, translation, and stability [1, 2, 3]. Identification of a consensus UUAUUUAU sequence in the 3′ UTRs of human and mouse mRNAs encoding tumor necrosis factor (TNF-α) and a variety of other inflammatory mediators led to the suggestion that these AU-rich elements AREs) could be important for regulating gene expression [4]. Subsequent studies confirmed that these and other AREs interact with ARE-binding proteins such as AUF1 (also known as hnRNPD), HuR and other Hu family proteins, and the CCCH zinc finger-containing RBPs ZFP36 (tristetraprolin), ZFP36L1, and ZFP36L2 [5], to alter mRNA degradation and protein expression [6]. In most cases, AREs have been reported to destabilize mRNAs, although in some cellular contexts certain AREs and ARE-binding proteins have been shown to stabilize mRNAs [6, 7]. Subsequent analyses of the human genome concluded that as many as 58% of human genes code for mRNAs that contain AREs [8, 9, 10], suggesting that these elements play a major role in regulating expression of a large group of genes."[2]

Interactions

Main article: Interaction gene transcriptions

"Chen and Shyu [11] divided AREs into two classes of AUUUA-containing AREs and a third class of non-AUUUA AREs. Class I AUUUA-containing AREs had 1-3 copies of scattered AUUUA motifs coupled with a nearby U-rich region or U stretch, whereas class II AUUUA-containing AREs had at least two overlapping copies of the nonamer UUAUUUA(U/A)(U/A) in a U-rich region. Non-AUUUA AREs had a U-rich region and other unknown features, and the relationship of these sequences to AUUUA-containing AREs remains poorly understood. Subsequent studies based on analyses of a set of 4884 AUUUA-containing AREs led to a new classification based primarily on the number of overlapping AUUUA-repeats [8, 9, 10]. This classification system, with five clusters distinguished by the number of repeats, was used to identify AUUUA-containing AREs in the human genome. AREs identified using this classification were found to be abundant in 3′ UTRs of human genes."[2]

Consensus sequences

Main article: Consensus sequence gene transcriptions

WWWUAUUUAUWW=(A/T)(A/T)(A/T)TATTTAT(A/T)(A/T).[1]

Binding site for

Constitutive "decay elements (CDEs) [4, 18][...] are conserved stem loop motifs that bind to the proteins Roquin and Roquin2, resulting in increased mRNA decay [18]. CDEs include an upper stem-loop sequence of the form UUCYRYGAA flanked by lower stem sequences. Lower stem sequences are formed by 2-5 nt pairs of reverse-complementary sequences (e.g. CCUUCYRYGAAGG has a lower stem length of 2)."[2]

CCUUCYRYGAAGG is CCTTC(C/T)(A/G)(C/T)GAAGG, and UUCYRYGAA is TTC(C/T)(A/G)(C/T)GAA.

Adenylate–uridylate rich element (Bakheet) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence (A/T)(A/T)(A/T)TATTTAT(A/T)(A/T) and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence (A/T)(A/T)(A/T)TATTTAT(A/T)(A/T) (starting with SuccessablesAURE.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for (A/T)(A/T)(A/T)TATTTAT(A/T)(A/T), 1, TTTTATTTATTA at 4076.
  2. positive strand, negative direction, looking for (A/T)(A/T)(A/T)TATTTAT(A/T)(A/T), 0.
  3. positive strand, positive direction, looking for (A/T)(A/T)(A/T)TATTTAT(A/T)(A/T), 0.
  4. negative strand, positive direction, looking for (A/T)(A/T)(A/T)TATTTAT(A/T)(A/T), 0.
  5. complement, negative strand, negative direction, looking for (A/T)(A/T)(A/T)ATAAATA(A/T)(A/T), 0.
  6. complement, positive strand, negative direction, looking for (A/T)(A/T)(A/T)ATAAATA(A/T)(A/T), 1, AAAATAAATAAT at 4076.
  7. complement, positive strand, positive direction, looking for (A/T)(A/T)(A/T)ATAAATA(A/T)(A/T), 0.
  8. complement, negative strand, positive direction, looking for (A/T)(A/T)(A/T)ATAAATA(A/T)(A/T), 0.
  9. inverse complement, negative strand, negative direction, looking for (A/T)(A/T)ATAAATA(A/T)(A/T)(A/T), 0.
  10. inverse complement, positive strand, negative direction, looking for (A/T)(A/T)ATAAATA(A/T)(A/T)(A/T), 1, AAATAAATAATA at 4077.
  11. inverse complement, positive strand, positive direction, looking for (A/T)(A/T)ATAAATA(A/T)(A/T)(A/T), 0.
  12. inverse complement, negative strand, positive direction, looking for (A/T)(A/T)ATAAATA(A/T)(A/T)(A/T), 0.
  13. inverse negative strand, negative direction, looking for (A/T)(A/T)TATTTAT(A/T)(A/T)(A/T), 1, TTTATTTATTAT at 4077.
  14. inverse positive strand, negative direction, looking for (A/T)(A/T)TATTTAT(A/T)(A/T)(A/T), 0.
  15. inverse positive strand, positive direction, looking for (A/T)(A/T)TATTTAT(A/T)(A/T)(A/T), 0.
  16. inverse negative strand, positive direction, looking for (A/T)(A/T)TATTTAT(A/T)(A/T)(A/T), 0.

Adenylate–uridylate rich element (Bakheet) UTRs

Main article: UTR promoter gene transcriptions

Negative strand, negative direction: TTTTATTTATTA at 4076.

Positive strand, negative direction: AAATAAATAATA at 4077.

Adenylate–uridylate rich element (Bakheet) random dataset samplings

  1. AUREr0: 0.
  2. AUREr1: 0.
  3. AUREr2: 0.
  4. AUREr3: 0.
  5. AUREr4: 0.
  6. AUREr5: 1, AATTATTTATTT at 859.
  7. AUREr6: 0.
  8. AUREr7: 0.
  9. AUREr8: 0.
  10. AUREr9: 0.
  11. AUREr0ci: 1, TAATAAATAAAA at 1499.
  12. AUREr1ci: 0.
  13. AUREr2ci: 0.
  14. AUREr3ci: 0.
  15. AUREr4ci: 0.
  16. AUREr5ci: 0.
  17. AUREr6ci: 0.
  18. AUREr7ci: 0.
  19. AUREr8ci: 0.
  20. AUREr9ci: 0.

AUREr distal promoters

Main article: Distal promoter gene transcriptions
  1. AUREr0ci: TAATAAATAAAA at 1499.


  1. AUREr5: AATTATTTATTT at 859.

ATTTA (Chen and Shyu, Class I) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence ATTTA and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence ATTTA (starting with SuccessablesAURS.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for ATTTA, 3, ATTTA at 4073, ATTTA at 2636, ATTTA at 1698.
  2. positive strand, negative direction, looking for ATTTA, 1, ATTTA at 4535.
  3. positive strand, positive direction, looking for ATTTA, 1, ATTTA at 3428.
  4. negative strand, positive direction, looking for ATTTA, 1, ATTTA at 4135.
  5. complement, negative strand, negative direction, looking for TAAAT, 1, TAAAT at 4535.
  6. complement, positive strand, negative direction, looking for TAAAT, 3, TAAAT at 4073, TAAAT at 2636, TAAAT at 1698.
  7. complement, positive strand, positive direction, looking for TAAAT, 1, TAAAT at 4135.
  8. complement, negative strand, positive direction, looking for TAAAT, 1, TAAAT at 3428.
  9. inverse complement, negative strand, negative direction, looking for TAAAT, 1, TAAAT at 4535.
  10. inverse complement, positive strand, negative direction, looking for TAAAT, 3, TAAAT at 4073, TAAAT at 2636, TAAAT at 1698.
  11. inverse complement, positive strand, positive direction, looking for TAAAT, 1, TAAAT at 4135.
  12. inverse complement, negative strand, positive direction, looking for TAAAT, 1, TAAAT at 3428.
  13. inverse negative strand, negative direction, looking for ATTTA, 3, ATTTA at 4073, ATTTA at 2636, ATTTA at 1698.
  14. inverse positive strand, negative direction, looking for ATTTA, 1, ATTTA at 4535.
  15. inverse positive strand, positive direction, looking for ATTTA, 1, ATTTA at 3428.
  16. inverse negative strand, positive direction, looking for ATTTA, 1, ATTTA at 4135.

ATTTA UTRs

Main article: UTR promoter gene transcriptions

Negative strand, negative direction: ATTTA at 4073.

Positive strand, negative direction: ATTTA at 4535.

ATTTA proximal promoters

Main article: Proximal promoter gene transcriptions

Negative strand, negative direction: ATTTA at 2636.

Negative strand, positive direction: ATTTA at 4135.

ATTTA distal promoters

Main article: Distal promoter gene transcriptions

Negative strand, negative direction: ATTTA at 1698.

Positive strand, positive direction: ATTTA at 3428.

AURS random dataset samplings

  1. AURSr0: 2, ATTTA at 2391, ATTTA at 752.
  2. AURSr1: 4, ATTTA at 3611, ATTTA at 3096, ATTTA at 1872, ATTTA at 1004.
  3. AURSr2: 9, ATTTA at 4144, ATTTA at 3617, ATTTA at 3485, ATTTA at 2895, ATTTA at 2520, ATTTA at 2131, ATTTA at 1771, ATTTA at 996, ATTTA at 129.
  4. AURSr3: 7, ATTTA at 4287, ATTTA at 4027, ATTTA at 2327, ATTTA at 1559, ATTTA at 1088, ATTTA at 797, ATTTA at 359.
  5. AURSr4: 8, ATTTA at 3863, ATTTA at 3723, ATTTA at 3027, ATTTA at 1676, ATTTA at 1300, ATTTA at 560, ATTTA at 403, ATTTA at 121.
  6. AURSr5: 8, ATTTA at 4055, ATTTA at 3718, ATTTA at 3629, ATTTA at 2630, ATTTA at 1313, ATTTA at 1110, ATTTA at 856, ATTTA at 490.
  7. AURSr6: 11, ATTTA at 4372, ATTTA at 3761, ATTTA at 3748, ATTTA at 3622, ATTTA at 2763, ATTTA at 2729, ATTTA at 1144, ATTTA at 1140, ATTTA at 916, ATTTA at 483, ATTTA at 187.
  8. AURSr7: 5, ATTTA at 3914, ATTTA at 2978, ATTTA at 2766, ATTTA at 1527, ATTTA at 330.
  9. AURSr8: 5, ATTTA at 2244, ATTTA at 1043, ATTTA at 828, ATTTA at 729, ATTTA at 195.
  10. AURSr9: 5, ATTTA at 3116, ATTTA at 1101, ATTTA at 968, ATTTA at 809, ATTTA at 623.

The complement inverse is the same as the complement which means the above results would repeat as their complements in the real sequences.

AURSr UTRs

Main article: UTR promoter gene transcriptions
  1. AURSr2: ATTTA at 4144, ATTTA at 3617, ATTTA at 3485, ATTTA at 2895.
  2. AURSr4: ATTTA at 3863, ATTTA at 3723, ATTTA at 3027.
  3. AURSr6: 11, ATTTA at 4372, ATTTA at 3761, ATTTA at 3748, ATTTA at 3622.

AURSr core promoters

Main article: Core promoter gene transcriptions
  1. AURSr3: ATTTA at 4287.

RDr proximal promoters

Main article: Proximal promoter gene transcriptions
  1. AURSr6: ATTTA at 2763, ATTTA at 2729.


  1. AURSr5: ATTTA at 4055.

AURSr distal promoters

Main article: Distal promoter gene transcriptions
  1. AURSr0: ATTTA at 2391, ATTTA at 752.
  2. AURSr2: ATTTA at 2520, ATTTA at 2131, ATTTA at 1771, ATTTA at 996, ATTTA at 129.
  3. AURSr4: ATTTA at 1676, ATTTA at 1300, ATTTA at 560, ATTTA at 403, ATTTA at 121.
  4. AURSr6: ATTTA at 1144, ATTTA at 1140, ATTTA at 916, ATTTA at 483, ATTTA at 187.
  5. AURSr8: ATTTA at 2244, ATTTA at 1043, ATTTA at 828, ATTTA at 729, ATTTA at 195.


  1. AURSr1: ATTTA at 3611, ATTTA at 3096, ATTTA at 1872, ATTTA at 1004.
  2. AURSr3: ATTTA at 4027, ATTTA at 2327, ATTTA at 1559, ATTTA at 1088, ATTTA at 797, ATTTA at 359.
  3. AURSr5: ATTTA at 3718, ATTTA at 3629, ATTTA at 2630, ATTTA at 1313, ATTTA at 1110, ATTTA at 856, ATTTA at 490.
  4. AURSr7: ATTTA at 3914, ATTTA at 2978, ATTTA at 2766, ATTTA at 1527, ATTTA at 330.
  5. AURSr9: 5, ATTTA at 3116, ATTTA at 1101, ATTTA at 968, ATTTA at 809, ATTTA at 623.

UUAUUUA(U/A)(U/A) (Chen and Shyu, Class II) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence TTATTTATT and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or one between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence TTATTTA(A/T)(A/T) (starting with SuccessablesUUA.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for TTATTTA(A/T)(A/T), 1, TTATTTATT at 4075.
  2. positive strand, negative direction, looking for TTATTTA(A/T)(A/T), 0.
  3. positive strand, positive direction, looking for TTATTTA(A/T)(A/T), 0.
  4. negative strand, positive direction, looking for TTATTTA(A/T)(A/T), 0.
  5. complement, negative strand, negative direction, looking for AATAAAT(A/T)(A/T), 0.
  6. complement, positive strand, negative direction, looking for AATAAAT(A/T)(A/T), 1, AATAAATAA at 4075.
  7. complement, positive strand, positive direction, looking for AATAAAT(A/T)(A/T), 0.
  8. complement, negative strand, positive direction, looking for AATAAAT(A/T)(A/T), 0.
  9. inverse complement, negative strand, negative direction, looking for (A/T)(A/T)TAAATAA, 0.
  10. inverse complement, positive strand, negative direction, looking for (A/T)(A/T)TAAATAA, 1, AATAAATAA at 4075.
  11. inverse complement, positive strand, positive direction, looking for (A/T)(A/T)TAAATAA, 0.
  12. inverse complement, negative strand, positive direction, looking for (A/T)(A/T)TAAATAA, 0.
  13. inverse negative strand, negative direction, looking for (A/T)(A/T)ATTTATT, 1, TTATTTATT at 4075.
  14. inverse positive strand, negative direction, looking for (A/T)(A/T)ATTTATT, 0.
  15. inverse positive strand, positive direction, looking for (A/T)(A/T)ATTTATT, 0.
  16. inverse negative strand, positive direction, looking for (A/T)(A/T)ATTTATT, 0.

UUA UTRs

Main article: UTR promoter gene transcriptions

Negative strand, negative direction: TTATTTATT at 4075.

UUA random dataset samplings

  1. UUAr0: 0.
  2. UUAr1: 0.
  3. UUAr2: 0.
  4. UUAr3: 0.
  5. UUAr4: 0.
  6. UUAr5: 2, TTATTTAAT at 3631, TTATTTATT at 858.
  7. UUAr6: 0.
  8. UUAr7: 0.
  9. UUAr8: 0.
  10. UUAr9: 0.
  11. UUAr0ci: 1, AATAAATAA at 1497.
  12. UUAr1ci: 0.
  13. UUAr2ci: 0.
  14. UUAr3ci: 0.
  15. UUAr4ci: 0.
  16. UUAr5ci: 0.
  17. UUAr6ci: 0.
  18. UUAr7ci: 1, TATAAATAA at 3632.
  19. UUAr8ci: 0.
  20. UUAr9ci: 0.

UUAr distal promoters

Main article: Distal promoter gene transcriptions
  1. UUAr0ci: AATAAATAA at 1497.


  1. UUAr5: TTATTTAAT at 3631, TTATTTATT at 858.
  2. UUAr7ci: TATAAATAA at 3632.

Constitutive decay element samplings

Main article: Model samplings

Copying a responsive elements consensus sequence TTC(C/T)(A/G)(C/T)GAA and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence TTC(C/T)(A/G)(C/T)GAA (starting with SuccessablesCDE.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for TTC(C/T)(A/G)(C/T)GAA, 0.
  2. positive strand, negative direction, looking for TTC(C/T)(A/G)(C/T)GAA, 0.
  3. positive strand, positive direction, looking for TTC(C/T)(A/G)(C/T)GAA, 1, TTCCATGAA at 128.
  4. negative strand, positive direction, looking for TTC(C/T)(A/G)(C/T)GAA, 0.
  5. complement, negative strand, negative direction, looking for AAG(A/G)(C/T)(A/G)CTT, 0.
  6. complement, positive strand, negative direction, looking for AAG(A/G)(C/T)(A/G)CTT, 0.
  7. complement, positive strand, positive direction, looking for AAG(A/G)(C/T)(A/G)CTT, 0.
  8. complement, negative strand, positive direction, looking for AAG(A/G)(C/T)(A/G)CTT, 1, AAGGTACTT at 128.
  9. inverse complement, negative strand, negative direction, looking for TTC(A/G)(C/T)(A/G)GAA, 0.
  10. inverse complement, positive strand, negative direction, looking for TTC(A/G)(C/T)(A/G)GAA, 0.
  11. inverse complement, positive strand, positive direction, looking for TTC(A/G)(C/T)(A/G)GAA, 0.
  12. inverse complement, negative strand, positive direction, looking for TTC(A/G)(C/T)(A/G)GAA, 0.
  13. inverse negative strand, negative direction, looking for AAG(C/T)(A/G)(C/T)CTT, 0.
  14. inverse positive strand, negative direction, looking for AAG(C/T)(A/G)(C/T)CTT, 0.
  15. inverse positive strand, positive direction, looking for AAG(C/T)(A/G)(C/T)CTT, 0.
  16. inverse negative strand, positive direction, looking for AAG(C/T)(A/G)(C/T)CTT, 0.

CDE distal promoters

Main article: Distal promoter gene transcriptions

Positive strand, positive direction: TTCCATGAA at 128.

CDE random dataset samplings

  1. CDEr0: 0.
  2. CDEr1: 0.
  3. CDEr2: 0.
  4. CDEr3: 0.
  5. CDEr4: 0.
  6. CDEr5: 0.
  7. CDEr6: 0.
  8. CDEr7: 0.
  9. CDEr8: 1, TTCCATGAA at 1472.
  10. CDEr9: 1, TTCTATGAA at 2350.
  11. CDEr0ci: 0.
  12. CDEr1ci: 0.
  13. CDEr2ci: 0.
  14. CDEr3ci: 0.
  15. CDEr4ci: 1, TTCGCGGAA at 2553.
  16. CDEr5ci: 1, TTCGTGGAA at 633.
  17. CDEr6ci: 0.
  18. CDEr7ci: 0.
  19. CDEr8ci: 0.
  20. CDEr9ci: 0.

CDEr distal promoters

Main article: Distal promoter gene transcriptions
  1. CDEr8: TTCCATGAA at 1472.
  2. CDEr4ci: TTCGCGGAA at 2553.


  1. CDEr9: TTCTATGAA at 2350.
  2. CDEr5ci: 1, TTCGTGGAA at 633.

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Tala Bakheet, Bryan R. G. Williams, and Khalid S. A. Khabar (1 January 2003). "ARED 2.0: an update of AU-rich element mRNA database". Nucleic Acids Research. 31 (1): 421–423. doi:10.1093/nar/gkg023. Retrieved 23 March 2021.
  2. ↑ 2.0 2.1 2.2 David A. Siegel, Olivier Le Tonqueze, Anne Biton, Noah Zaitlen, and David J. Erle (12 February 2020). "Massively Parallel Analysis of Human 3′ UTRs Reveals that AU-Rich Element Length and Registration Predict mRNA Destabilization" (PDF). bioRxiv. doi:10.1101/2020.02.12.945063. Retrieved 23 March 2021.

External links

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