Question

In these imprinted cells, the SNRPN transcript overlaps with another gene, called UBE3A, which is transcribed in the opposite direction. This means that the region that the RNA polymerase transcribes in these two genes actually overlaps; in some cases, overlapping transcription in opposite directions leads to transcriptional interference, meaning that collisions between the polymerases traveling in opposite directions can interfere with transcription. It is believed that this takes place in this case, meaning that the more SNRPN transcription occurs, the more this disrupts transcription of UBE3A. Based on this information as well as information about the effects of imprinting on SNRPN transcription, which of the following statements about UBE3A transcription would be true?

The maternal copy of UBE3A is expressed and the paternal copy is silenced.

The paternal copy of UBE3A is expressed and the maternal copy is silenced.

Both copies of UBE3A are highly expressed.

Both copies of UBE3A are silenced.

Answer 1

E3 ubiquitin ligase protein 3a or UBE3A is a paternally imprinted gene in neurons that is expressed from the maternal allele. It is involved in the degradation of the p53 protein. This gene is not imprinted in non-neuronal tissues.

The promoter of UBE3A is not methylated in the CG rich region on any chromosomes- maternal or paternal. It is the paternal SNRPN gene that is methylated at the 3’ end. SNPRN is methylated in maternal chromosome and non-methylated in paternal chromosome. This gene codes for a long non-coding RNA that has the IPW loci.

This paternal non-coding RNA in neurons will overlap UBE3A as UBE3A-ATS RNA, which is anti-sense to UBE3A. This is known as transcriptional collision.

The paternal UBE3A gene promoter is transcribed by RNA polymerase at the 5’ end as it is unmethylated. However, there is decreased expression of UBE3A and UBE3A-ATS (3’ end). This is because two RNA polymerases II transcribing UBE3A and UBE3A-ATS collide with each other at intron 4 of UBE3A. As a result of this collision, the RNA polymerase will either dissociate or stall at intron 4. This causes termination of transcription of both sense Ube3a and anti-sense Ube3a-ATS. The preformed Ube3a transcript at 5' end is then degraded. This will cause silencing of the UBE3A allele on the paternal chromosome. The maternal Ube3a-ATS is maternally silences by imprinting. As no Ube3a-ATS is produced, there is no transcriptional collision, allowing expression of Ube3a form the maternal chromosome. Thus, UBE3A is paternally silenced while maternal copy is transcriptionally active. Either maternal or paternal copies are expressed in imprinted genes.

Right choice: The maternal copy of UBE3A is expressed and the paternal copy is silenced.