NDLI: The association of Alu repeats with the generation of potential AU-rich elements (ARE) at 3' untranslated regions.

Content Provider	Springer Nature : BioMed Central
Author	An, Hyeong Jun Lee, Doheon Lee, Kwang Hyung Bhak, Jonghwa
Abstract	Background A significant portion (about 8% in the human genome) of mammalian mRNA sequences contains AU (Adenine and Uracil) rich elements or AREs at their 3' untranslated regions (UTR). These mRNA sequences are usually stable. However, an increasing number of observations have been made of unstable species, possibly depending on certain elements such as Alu repeats. ARE motifs are repeats of the tetramer AUUU and a monomer A at the end of the repeats ((AUUU)nA). The importance of AREs in biology is that they make certain mRNA unstable. Proto-oncogene, such as c-fos, c-myc, and c-jun in humans, are associated with AREs. Although it has been known that the increased number of ARE motifs caused the decrease of the half-life of mRNA containing ARE repeats, the exact mechanism is as of yet unknown. We analyzed the occurrences of AREs and Alu and propose a possible mechanism for how human mRNA could acquire and keep AREs at its 3' UTR originating from Alu repeats. Results Interspersed in the human genome, Alu repeats occupy 5% of the 3' UTR of mRNA sequences. Alu has poly-adenine (poly-A) regions at its end, which lead to poly-thymine (poly-T) regions at the end of its complementary Alu. It has been found that AREs are present at the poly-T regions. From the 3' UTR of the NCBI's reference mRNA sequence database, we found nearly 40% (38.5%) of ARE (Class I) were associated with Alu sequences (Table 1) within one mismatch allowance in ARE sequences. Other ARE classes had statistically significant associations as well. This is far from a random occurrence given their limited quantity. At each ARE class, random distribution was simulated 1,000 times, and it was shown that there is a special relationship between ARE patterns and the Alu repeats. Symbol ARE sequence Class I (AUUU)5A AUUUAUUUAUUUAUUUAUUUA Class II (AUUU)4A AUUUAUUUAUUUAUUUA Class III U(AUUU)3AU UAUUUAUUUAUUUAU Class IV UU(AUUU)2AUU UUAUUUAUUUAUU Class V U4AUUUAU4 UUUUAUUUAUUUU Class VI W3UAUUUAUW3 WWWUAUUUAWWW Table 1 Defined ARE classes. (Symbol marks are used in this study instead of full sequences.) Conclusion AREs are mediating sequence elements affecting the stabilization or degradation of mRNA at the 3' untranslated regions. However, AREs' mechanism and origins are unknown. We report that Alu is a source of ARE. We found that half of the longest AREs were derived from the poly-T regions of the complementary Alu.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/1471-2164-5-97.pdf
Ending Page	5
Page Count	5
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/1471-2164-5-97
Journal	BMC Genomics
Issue Number	1
Volume Number	5
Language	English
Publisher	BioMed Central
Publisher Date	2004-12-21
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics mRNA Sequence Random Sequence Generation mRNA Decay Rate Potential AREs Find Repeat Sequence
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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