Gvozdenov Z, Barcutean Z, Struhl K

Mol Cell. 2023 Apr 24:S1097-2765(23)00254-X. 10.1016/j.molcel.2023.04.010

Functional analysis of a random-sequence chromosome reveals a high level and the molecular nature of transcriptional noise in yeast cells

Circular chromosome of 27 kbp comprising 18 kbp of random sequences. “the major class of nucleosomes average 147 bp (range 143–180), i.e., the expected size” “nucleosome occupancy on [the artificial chromosome] is 1.42-fold higher than on yeast genomic DNA” “when compared with yeast genomic chromatin, [artificial] chro- matin is characterized by fewer [nucleotide-depleted regions], fewer highly positioned nucleosomes, and little nucleosome phasing, although nucleosome positioning is nonrandom.” “Transcription from all regions of random-sequence DNA leads to similar RNA levels that are roughly comparable to that of the majority of mRNA expressed from yeast genomic DNA” “transcription from randomsequence DNA is more variable than from genomic DNA” “decay rates of RNAs expressed from randomsequence DNA are 3-fold faster” “RNAs expressed from [the artificial chrmosome] are polyadenylated throughout the entire region of random-sequence DNA” “the choice of poly(A) sites by the cleavage/polyadenylation machinery is roughly similar for RNAs expressed from random-sequence and genomic DNAs.” “The 50 isoform pattern from random-sequence DNA resembles that observed from yeast genomic regions not corresponding to 50 UTRs” “The level of newly synthesized RNA from random-sequence DNA is in excellent accord with calculated estimates that only 10%–20% of elongating RNA Pol II molecules generate mRNAs, such the remaining 80%–90% represent transcriptional noise”