The fidelity of transcription in human cells

To determine the error rate of transcription in human cells, we analyzed the transcriptome of H1 human embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing of the transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species in human cells. Our results indicate that different RNA species display different error rates, suggesting that human cells prioritize the fidelity of some RNAs over others. Cross-referencing the errors that we detected with various genetic and epigenetic features of the human genome revealed that the in vivo error rate in human cells changes along the length of a transcript and is further modified by genetic context, repetitive elements, epigenetic markers, and the speed of transcription. Our experiments further suggest that BRCA1, a DNA repair protein implicated in breast cancer, has a previously unknown role in the suppression of transcription errors. Finally, we analyzed the distribution of transcription errors in multiple tissues of a new mouse model and found that they occur preferentially in neurons, compared to other cell types. These observations lend additional weight to the idea that transcription errors play a key role in the progression of various neurological disorders, including Alzheimer's disease.

Automated summary

To determine the error rate of transcription in human cells, researchers analyzed the transcriptome of H1 human embryonic stem cells using a high-fidelity circle-sequencing approach. They found approximately 100,000 errors in major RNA species, indicating that different RNA species have different error rates. Cross-referencing the errors with genetic and epigenetic features revealed that the error rate changes along the transcript length and is modified by genetic context, repetitive elements, and epigenetic markers. The study also discovered a novel role of BRCA1 in suppressing transcription errors and found that transcription errors preferentially occur in neurons, suggesting their involvement in neurological disorders.