Central Dogma of Molecular Biology

In any given cell, DNA carries genetic information, and proteins perform cellular functions. The transfer of information stored in DNA and its conversion into functional molecules occurs in two stages: transcription, in which DNA is copied into mRNA; and translation, in which mRNA is translated into proteins. The central dogma of molecular biology postulates that RNA is a perfectly faithful copy of DNA, the RNA sequence is predictable, the genetic code is universal, and, therefore, the DNA sequence predicts the sequences of all proteins.

Discovery of RDDs by GENCLIS

When DNA is copied into mRNA, three types of errors can occur:
1) Base substitution: the complementary base is not inserted; instead, the base that precedes or follows the said base replaces it;
2) Gap: the complementary base is omitted; and
3) Insertion: a supernumerary base is added.
As a result of these errors, there exists a non-negligible proportion of mRNA whose message is no longer complementary to the DNA sequence. These mRNAs are translated into proteins, whose amino acid sequences are not determined by the DNA sequence, thus contributing to protein diversity.
Transcriptional Infidelity (TI) is a normal phenomenon that occurs at higher rates in cancer. This phenomenon does not occur randomly, but depends on the context of DNA.

DNA is transcribed into RNA by RNA polymerase II. The RNA is then translated into protein.

During a TI event, RNA polymerase introduces errors in the RNA sequence.

Base Substitution:

This term refers to the replacement of one base by another. The translation of RNA carrying base substitutions leads to the synthesis of a protein with a modified sequence.
Changes in the amino acid sequences of proteins translated from RNA variants lead to a gain or loss of function.

Base Deletion:

The consequences of a base deletion for the protein sequence are much more significant than those of a base substitution. A base deletion results in a shift of the reading frame of the protein.
As a result, both the composition and size of the protein sequence are modified. These modifications in the amino acid sequence confer specific physicochemical and immunogenic properties to the protein variants.

The transcription infidelity as described above is available in multiple fields of clinical applications