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Characterization of piRNAs Across Postnatal Development in Mouse Brain


Characterization of piRNAs Across Postnatal Development in Mouse Brain

Yanal Ghosheh et al. Sci Rep.


PIWI-interacting RNAs (piRNAs) are responsible for maintaining the genome stability by silencing retrotransposons in germline tissues- where piRNAs were first discovered and thought to be restricted. Recently, novel functions were reported for piRNAs in germline and somatic cells. Using deep sequencing of small RNAs and CAGE of postnatal development of mouse brain, we identified piRNAs only in adult mouse brain. These piRNAs have similar sequence length as those of MILI-bound piRNAs. In addition, we predicted novel candidate regulators and putative targets of adult brain piRNAs.


Figure 1
Figure 1. Sequencing of piRNA in brain and testes.
(a) Bar plot shows the number of sequenced reads; reads that mapped to genome; and reads mapped within annotated piRNA clusters. (b) Sequence bias of reads obtained in each stage and tissue; unlike reads at adult stage in brain, reads at 10 dpp and 14 dpp lack significant 1U bias, all reads from testes samples showed significant 1U bias. Sequence logo was obtained using Weblogo.
Figure 2
Figure 2. Expression profile of piRNA clusters in brain and testes clusters.
(a) Heatmap showing expression profiles of piRNA clusters (rows); brain adult sample cluster with testes adult sample (based on Pearson correlation), suggesting they share expressed piRNA clusters; annotation at the left of heatmap shows that most piRNA clusters expressed in adult brain (BT clusters) are intergenic (b) boxplot showing distributions of coverage correlation that was computed along the length of expressed piRNA between all samples; high correlation indicate that piRNAs production along the length of piRNAS clusters is similar across all conditions.
Figure 3
Figure 3. piRNAs in adult brain are similar be MILI-bound.
(a) Length distribution of piRNAs at adult brain reveals a peak at 26~27 bases which is commonly associated with MILI-binding. Consistent with current knowledge, A high peak at 29~31 bases in adult testes and a smaller peak at 26~27 bases are associated with MIWI- and MILI-binding, respectively.
Figure 4
Figure 4. Identification of candidate regulators of BT piRNA clusters.
(a) Expression profile of Mybl1. (b) Diagram depicting the first possible scenarios in which BT clusters are expressed due to an activator TF. (c) Similar to (b) but for second scenario, in which non-BT clusters are silenced in adult brain due to a repressor TF. (d) Expression profile of candidate TFs that fit first scenario. (e) Expression profile of candidate TFs that fit the second scenario. (f) Co-expression network obtained from GeneMANIA showing that many candidates co-express with Mybl1; TFs were classified as activator or a repressor based on our suggested scenarios as their assumed function in the scenarios does not contradict with known literature about their function.

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