The piRNA pathway sustains adult neurogenesis by reducing protein synthesis and cellular senescence

Gasperini, Caterina; Tuntevski, Kiril; Pelizzoli, Roberta; Van, Amanda Lo; Mangoni, Damiano; Cossu, Rosa Maria; Pascarella, Giovanni; Bianchini, Paolo; Bielefeld, Pascal; Scarpato, Margherita; Pons-Espinal, Meritxell; Sanges, Remo; Diaspro, Alberto; Fitzsimons, Carlos P.; Carninci, Piero; Gustincich, Stefano; Tonelli, Davide De Pietri

doi:10.1101/2020.09.15.297739

Cited by 6 publications

(5 citation statements)

References 76 publications

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“…In the current study, PIWIL2 expression was not detected in sALS postmortem samples, supporting the observation by Gasparini et al [25]that PIWIL2 is expressed in neural stem/ progenitor cells, but not in neurons. PIWIL3 also was not detected by immunoblotting in these samples, while PIWIL4 was downregulated by 0.5-0.6-fold in most sALS samples.…”

Section: Piwi Protein Dysregulation As a Potential Cause Of Alssupporting

confidence: 92%

piRNA/ PIWI protein complex as potential biomarkers in sporadic amyotrophic lateral sclerosis

Abdelhamid

Ogawa

Beck

et al. 2021

Preprint

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The pathological hallmark in the majority of amyotrophic lateral sclerosis (ALS) cases is the mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein. Several studies have attributed disease processes of ALS to abnormal RNA metabolism. However, dysregulated biogenesis of RNA, especially non-coding RNA (ncRNA), is poorly understood. To resolve it, RNA-Seq, biochemical and immunohistochemical analyses were performed on sporadic ALS (sALS) and control postmortem brain samples. Here we report perturbation of ncRNA biogenesis in PIWI-interacting RNA (piRNA) in several sALS brain samples associated with TDP-43 pathology. In addition, we confirmed the dysregulation of two PIWI homologs, PIWI-like-mediated gene silencing 1 (PIWIL1) and PIWIL4, which bind to piRNAs to regulate their expression. PIWIL1 was mislocalized and co-localized with TDP-43 in motor neurons of sporadic ALS lumbar cords. Our results imply that dysregulation of piRNA, PIWIL1, and PIWIL4 is linked to pathogenesis of ALS. Based on these results, piRNAs and PIWI proteins are expected to be potential diagnostic biomarkers and therapeutic targets of ALS.

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Section: Piwi Protein Dysregulation As a Potential Cause Of Alssupporting

confidence: 92%

piRNA/ PIWI protein complex as potential biomarkers in sporadic amyotrophic lateral sclerosis

Abdelhamid

Ogawa

Beck

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In the current study, PIWIL2 expression was not detected in sALS postmortem samples, supporting the observation by Gasparini et al [26], that PIWIL2 is expressed in neural stem/progenitor cells, but not in neurons. PIWIL3 also was not detected by immunoblotting in these samples, while PIWIL4 was downregulated by 0.5-0.6-fold in most sALS samples.…”

Section: Piwi Protein Dysregulation As a Potential Cause Of Alssupporting

confidence: 92%

piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis

et al. 2022

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The pathological hallmark of the majority of amyotrophic lateral sclerosis (ALS) cases is the mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein. Several studies have attributed disease processes of ALS to abnormal RNA metabolism. However, dysregulated biogenesis of RNA, especially non-coding RNA (ncRNA), is poorly understood. To resolve it, RNA-Seq, biochemical, and immunohistochemical analyses were performed on the pyramidal tract of the medulla oblongata of sporadic ALS (sALS) and control postmortem brain samples. Here, we report perturbation of ncRNA biogenesis in PIWI-interacting RNA (piRNA) in several sALS brain samples associated with TDP-43 pathology. In addition, we confirmed the dysregulation of two PIWI homologs, PIWI-like-mediated gene silencing 1 (PIWIL1) and PIWIL4, which bind to piRNAs to regulate their expression. PIWIL1 was mislocalized and co-localized with TDP-43 in motor neurons of sporadic ALS lumbar cords. Our results imply that dysregulation of piRNA, PIWIL1, and PIWIL4 is linked to pathogenesis of ALS. Based on these results, piRNAs and PIWI proteins are potential diagnostic biomarkers and therapeutic targets of ALS.

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“…Interestingly, the hippocampus shows the highest number of unique piRNA sequences and piRNA transcripts (5494 piRNAs) in the adult brain (Perera et al, 2019 ). In agreement with this observation, it was recently demonstrated that the piRNA pathway has a crucial role in maintaining the homeostasis and the fate of hippocampal NSCs (Gasperini et al, 2021 ). In particular, the expression of MILI and piRNAs was found to be enriched in NPCs of the postnatal mouse hippocampus, compared to their differentiated progeny, and piRNA functions were shown to be essential for neurogenesis.…”

Section: Piwi-interacting Rnas and Other Classes Of Sncrnassupporting

confidence: 62%

“…In particular, the expression of MILI and piRNAs was found to be enriched in NPCs of the postnatal mouse hippocampus, compared to their differentiated progeny, and piRNA functions were shown to be essential for neurogenesis. Moreover, inhibition of the piRNA pathway in adult NPCs leads to senescence-associated inflammation and an increase in reactive astrogliogenesis (Gasperini et al, 2021 ), a condition which has been linked to age-related impairment of neurogenesis and neurodegeneration.…”

Section: Piwi-interacting Rnas and Other Classes Of Sncrnasmentioning

confidence: 99%

Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications

Penning

Tosoni

Abiega

et al. 2022

Front. Cell. Neurosci.

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The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a multitude of intracellular, juxtacrine, and paracrine signals and biological pathways. Within the niches, adult neural stem cells (aNSCs) generate astrocytic and neuronal progeny, with the latter predominating in physiological conditions. The new neurons generated from this neurogenic process are functionally linked to memory, cognition, and mood regulation, while much less is known about the functional contribution of aNSC-derived newborn astrocytes and adult-born oligodendrocytes. Accumulating evidence suggests that the deregulation of aNSCs and their progeny can impact, or can be impacted by, aging and several brain pathologies, including neurodevelopmental and mood disorders, neurodegenerative diseases, and also by insults, such as epileptic seizures, stroke, or traumatic brain injury. Hence, understanding the regulatory underpinnings of aNSC activation, differentiation, and fate commitment could help identify novel therapeutic avenues for a series of pathological conditions. Over the last two decades, small non-coding RNAs (sncRNAs) have emerged as key regulators of NSC fate determination in the adult neurogenic niches. In this review, we synthesize prior knowledge on how sncRNAs, such as microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), may impact NSC fate determination in the adult brain and we critically assess the functional significance of these events. We discuss the concepts that emerge from these examples and how they could be used to provide a framework for considering aNSC (de)regulation in the pathogenesis and treatment of neurological diseases.

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The piRNA pathway sustains adult neurogenesis by reducing protein synthesis and cellular senescence

Cited by 6 publications

References 76 publications

piRNA/ PIWI protein complex as potential biomarkers in sporadic amyotrophic lateral sclerosis

piRNA/ PIWI protein complex as potential biomarkers in sporadic amyotrophic lateral sclerosis

piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis

Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications

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