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. Author manuscript; available in PMC: 2020 Jul 2.
Published in final edited form as: Ann Integr Mol Med. 2020;2(1):90–114. doi: 10.33597/aimm.02-1007

Figure 7: Design of RNA transcripts in experimental models expressing Aβ solely through RNA-dependent amplification of Aβ- or C99-encoding mRNA.

Figure 7:

Uppercase letters: Nucleotide sequence of the sense RNA. Lowercase letters: Nucleotide sequence of the antisense RNA. Highlighted in blue: Aβ- or C99- encoding region of mRNA. Highlighted in green: 5’AUG3’ or its complement on the opposite RNA strand. Highlighted in yellow: 3’-terminal complementary element, TCE, and internal complementary element, ICE, of the antisense RNA. Highlighted in gray: 3’-terminal “C” not enoded in the DNA, a transcript of the cap “G” of mRNA and matching “G” at the 5’ end of the ICE on the antisense RNA. Highlighted in red: Additional “AUG” codon in optimal translation initiation context, upstream of and out-of-frame with Aβ-encoding sequence. Red arrow: Position of cleavage of chimeric intermediate following strand separation. Top panel: A - RNA encoding Aβ or C99 fragment of βAPP; note that the “AUG” immediately preceding Aβ-coding sequence has been removed and replaced by the “ACA”, and there is no functional translation initiation codon in-frame with and upstream from Aβ-coding segment. B - Antisense RNA; note that it contains 5’aug3’ followed in the 3’ direction by sequence encoding N-terminus of Aβ at its 3’end. C - Antisense RNA folded into self-priming configuration; note that 5’aug3’ is accommodated by the 3’ugu5’, a complement of the “ACA” in the sense strand. D - Extension of self-primed antisense RNA generating chimeric intermediate containing covalently bound sense and antisense RNA strands; position of cleavage following strand separation is indicated by red arrow. E - Chimeric RNA end product of RNA-dependent mRNA amplification; note that it consists of the antisense portion encoding the “aug” translation initiation codon and the N-terminus of resulting polypeptide (Aβ or C99), whereas the sense RNA portion encodes the rest of a polypeptide and contains 3’UTR and 3’-terminal poly(A). Bottom panel: A - RNA encoding Aβ or C99 fragment of βAPP; note that it is preceded immediately by the “AUG” but also contains additional “AUG” codon in optimal translation initiation context, upstream of and out-of-frame with Aβ- or C99-encoding sequence. B - Antisense RNA. C - Antisense RNA folded into selfpriming configuration. D - Extension of self-primed antisense RNA generating chimeric intermediate; position of cleavage following strand separation is indicated by red arrow. E - Chimeric RNA end product of RNA-dependent mRNA amplification; note that it contains only one “AUG” translation initiation codon immediately preceding Aβ- or C99-coding sequence followed by the 3’UTR and 3’-terminal poly(A).